There are several types of amyloidosis classified according to the precursor protein involved. The most common type, AL amyloidosis, arises from plasma cells in the bone marrow producing abnormal immunoglobulin light chains. Familial amyloidosis can be inherited and results from mutations in proteins like transthyretin. Secondary amyloidosis, such as AA amyloidosis, develops due to chronic inflammatory conditions and causes amyloid to deposit in the kidneys and liver. Early and accurate diagnosis of the specific type of amyloidosis is important for determining appropriate treatment.
The aging process causes changes in cells and organs over time through a combination of genetic and environmental factors. As people age, cells divide more slowly, immune function declines, and regulation of cell death is disrupted. Physically, aging is associated with loss of height, weight gain until late adulthood, increased body fat, and slower reaction times. While some organ decline is normal, lifestyle factors influence diseases like heart disease and cataracts. The aging process varies between individuals.
Amyloidosis is characterized by the deposition of insoluble protein fibrils in tissues. There are different types based on the precursor protein, such as immunoglobulin light chain (AL), serum amyloid A (AA), and transthyretin (ATTR). In the kidney, amyloid deposits can involve the glomeruli, vessels, tubules, and interstitium. On microscopy, amyloid appears as an eosinophilic hyaline material that shows apple-green birefringence under polarized light after Congo red staining. Typing is important for management and involves immunohistochemistry for different precursor proteins. Treatment involves controlling the underlying condition driving amyloid formation and may include chemotherapy, transplantation, or controlling inflammation.
This document provides a review of renal amyloidosis. It begins by defining amyloidosis as a group of diseases caused by the misfolding and accumulation of various proteins. 27 human proteins are known to cause amyloidosis. The kidney is a common site of deposition for several types of amyloidosis. The document reviews the pathogenesis of amyloidosis, determinants of renal deposition, how it causes renal disease, classification, epidemiology including statistics from India, pathology findings including staining techniques, and methods to determine the type of amyloidosis involved.
Islamic Perspective on Nutrigenomic intervention in Postmenopausal Osteoporos...Hafizah R
Nutrigenomics is the study of the effects of foods and food constituents on gene expression. It is about how our DNA is transcribed into mRNA and then to proteins and provides a basis for understanding the biological activity of food components. The boundary between health and disease is often defined by a complex equilibrium between two elements, genetics and lifestyle.
The aim of nutrigenomics is to personalize nutrition and its effects on health by tailoring food to the individual genotype. The purpose of this review is to present the interaction between a genetic polymorphisms disorder which is Post-Menopausal Osteoporosis (PMO) and diet. Poor nutrition can be risk factor for diseases. Common dietary chemicals can act on the human genome, either directly or indirectly to alter gene expression or gene structure. The degree to which diet influences the balance between health and disease depends on an individual‟s genetic makeup.
This document discusses various theories of aging and approaches to anti-aging. It covers definitions of life span and life expectancy, various theories on what causes aging including evolutionary, molecular, cellular and systemic theories, and a clinical approach to aging including distinguishing true aging from disease and promoting positive aging through lifestyle factors and interventions.
The aging process causes changes in cells and organs over time through a combination of genetic and environmental factors. As people age, cells divide more slowly, immune function declines, and regulation of cell death is disrupted. Physically, aging is associated with loss of height, weight gain until late adulthood, increased body fat, and slower reaction times. While some organ decline is normal, lifestyle factors influence diseases like heart disease and cataracts. The aging process varies between individuals.
Amyloidosis is characterized by the deposition of insoluble protein fibrils in tissues. There are different types based on the precursor protein, such as immunoglobulin light chain (AL), serum amyloid A (AA), and transthyretin (ATTR). In the kidney, amyloid deposits can involve the glomeruli, vessels, tubules, and interstitium. On microscopy, amyloid appears as an eosinophilic hyaline material that shows apple-green birefringence under polarized light after Congo red staining. Typing is important for management and involves immunohistochemistry for different precursor proteins. Treatment involves controlling the underlying condition driving amyloid formation and may include chemotherapy, transplantation, or controlling inflammation.
This document provides a review of renal amyloidosis. It begins by defining amyloidosis as a group of diseases caused by the misfolding and accumulation of various proteins. 27 human proteins are known to cause amyloidosis. The kidney is a common site of deposition for several types of amyloidosis. The document reviews the pathogenesis of amyloidosis, determinants of renal deposition, how it causes renal disease, classification, epidemiology including statistics from India, pathology findings including staining techniques, and methods to determine the type of amyloidosis involved.
Islamic Perspective on Nutrigenomic intervention in Postmenopausal Osteoporos...Hafizah R
Nutrigenomics is the study of the effects of foods and food constituents on gene expression. It is about how our DNA is transcribed into mRNA and then to proteins and provides a basis for understanding the biological activity of food components. The boundary between health and disease is often defined by a complex equilibrium between two elements, genetics and lifestyle.
The aim of nutrigenomics is to personalize nutrition and its effects on health by tailoring food to the individual genotype. The purpose of this review is to present the interaction between a genetic polymorphisms disorder which is Post-Menopausal Osteoporosis (PMO) and diet. Poor nutrition can be risk factor for diseases. Common dietary chemicals can act on the human genome, either directly or indirectly to alter gene expression or gene structure. The degree to which diet influences the balance between health and disease depends on an individual‟s genetic makeup.
This document discusses various theories of aging and approaches to anti-aging. It covers definitions of life span and life expectancy, various theories on what causes aging including evolutionary, molecular, cellular and systemic theories, and a clinical approach to aging including distinguishing true aging from disease and promoting positive aging through lifestyle factors and interventions.
Hurler Syndrome is a rare genetic disorder caused by the absence of an enzyme that breaks down complex sugars, causing them to build up in the lysosome and produce severe symptoms. Sidney Van Hook, a three-year-old with Hurler Syndrome, received a bone marrow transplant which was successful but she still has some symptoms. New medications like Aldurazyme can replace the missing enzyme to stop sugar buildup and bone marrow transplants or gene therapy may help treat the disease.
The document summarizes Marfan syndrome, a genetic disorder that affects connective tissue. It is caused by mutations in the FBN1 gene and is inherited in an autosomal dominant pattern. Symptoms can include issues with the eyes, skeleton and cardiovascular system. Diagnosis is based on criteria from the 2010 Ghent revision and involves assessment of features like aortic root size and lens displacement. Untreated, it can lead to life-threatening complications such as aortic aneurysm or dissection.
Ehlers-Danlos syndrome (EDS) is a connective tissue disease caused by mutations in collagen genes. It affects connective tissues supporting skin, blood vessels, and organs. There are six main types classified by symptoms. EDS causes loose, elastic skin and fragile tissues, resulting in easy bruising and joint dislocations. While prevalence is estimated at 1 in 5,000, many cases may be undiagnosed. Treatment focuses on pain management, physical therapy, and managing complications.
Cancer is not a single disease, but rather many diseases where abnormal cells grow uncontrollably. There are over 100 types of cancer that can develop when cells in any part of the body start growing out of control. Risk factors for cancer include behaviors such as smoking, excessive alcohol consumption, poor diet, obesity, and lack of exercise. Early detection of cancer symptoms can help improve outcomes, as some cancers are curable if caught early. Leukemia is a type of cancer that affects the bone marrow and blood cells, crowding out normal cells and impairing the immune system. There are four main types of leukemia - acute, chronic, lymphocytic, and myelogenous - which differ in their rate of progression.
The document discusses amyloidosis, a group of disorders involving the deposition of abnormal proteins outside cells. There are different types including primary, secondary, systemic, localized, and hereditary amyloidosis. Secondary amyloidosis is the most common type and is caused by chronic inflammation. Clinically, amyloidosis can lead to organ enlargement and failure of the liver, kidneys, brain, and heart. Under the microscope, amyloid deposits appear as extracellular pink proteins that stain positive with Congo red and appear apple green under polarized microscopy.
Aubrey de Grey's Slide - Nigeria ICT Fest 2015nigeriaictfest
Top British gerontologist, Chief Science Officer, SENS research foundation and fellow at the Institute for Ethics and Emerging Technologies speaks about his research work on regenerative medicine at Nigeria ICT Fest 2015.
Ehlers Danlos Syndrome (EDS) is a genetic connective tissue disorder caused by defects in collagen. There are several types of EDS with varying symptoms. The hypermobility type involves loose joints and double-jointedness. Classical EDS affects the skin, causing easy bruising and scarring. The vascular type is the most severe and life-threatening due to risk of organ and blood vessel rupture. While there is no cure for EDS, physical therapy can help strengthen joints to prevent dislocation. Gene therapy may help EDS in the future by replacing or inactivating mutated genes.
Aubrey de grey why you're helpless now but not for longSelf Spark
This document discusses aging and age-related diseases. It notes that while infectious diseases have been prevented through sanitation, vaccines, antibiotics, and carrier control, age-related diseases have not. It describes aging as the lifelong accumulation of damage to tissues, cells, and molecules in the body from normal metabolic processes. This damage cannot be automatically reversed by the body and leads to disease and disability when too much damage accumulates. The document advocates for a maintenance approach to treating aging by repairing and preventing further damage as a way to significantly extend healthy lifespans. It provides examples of research into specific maintenance therapies and argues this approach could eliminate most age-related diseases.
Amyloidosis in head and neck manifestationYu-Fu Wu
This document summarizes amyloidosis, a condition characterized by extracellular deposition of fibrillary proteins. Amyloidosis can occur systemically or locally in organs. The deposition forms beta-sheet rich fibrils that take up Congo red dye, appearing apple-green under microscopy. Normally misfolded proteins are degraded, but in amyloidosis these quality control mechanisms fail, allowing accumulation. Systemic types include AL amyloidosis associated with multiple myeloma and AA amyloidosis in chronic infections/inflammation. Localized amyloidosis can affect the larynx in rare cases, presenting as slowly progressive dysphonia from diffuse thickening or discrete lesions.
This document discusses amyloidosis, which is the extracellular deposition of abnormal protein fibrils called amyloid in tissues and organs. Amyloidosis can be primary, meaning the deposition is in the disease itself, or secondary, as a complication of another underlying disease. Diagnosis involves biopsy and staining of tissues with Congo red dye to detect amyloid deposits. The kidney is a commonly affected organ where amyloid deposits are seen in the glomerular capillary tuft and surrounding tissues, which can lead to atrophy and impaired function.
This document provides an overview of amyloidosis, including:
- Amyloidosis is caused by the extracellular deposition of misfolded proteins forming fibrils. There are different types classified by the precursor protein involved.
- Systemic forms include AL amyloidosis associated with plasma cell disorders and AA amyloidosis associated with inflammatory conditions.
- Diagnosis involves biopsy of tissues like fat pad or organs stained with Congo red to identify amyloid deposits. Immunohistochemistry identifies the precursor protein type.
- Organ involvement varies but kidney, heart, liver and spleen are commonly affected. Clinical manifestations depend on the organs involved and may include proteinuria, heart failure, hepatomegaly or neurological symptoms.
This is a series of notes on general pathology.. Amyloidosis is a very important topic from exam point of view both for under and post graduates..topic is presented here with enough colour illustrations
Amyloidosis comprises a group of diseases characterized by the extracellular deposition of insoluble fibrous amyloid proteins in various body tissues. There are at least 20 different types of amyloid proteins that can form fibrils and deposit in tissues. The classification of amyloidosis has evolved from descriptive terms to designations based on the type of amyloid fibril protein involved (such as AL, AA, and TTR amyloidosis). AA amyloidosis is caused by deposition of amyloid A protein and is associated with long-term inflammatory conditions like familial Mediterranean fever. It commonly involves the kidneys and gastrointestinal tract and can lead to renal failure. Treatment focuses on managing the underlying inflammatory condition to reduce amyloid A protein levels and prevent further deposition.
amyloidosis(including history,physical and chemical properties, classification, variants, staining characteristics, lab diagnosis,morphological patterns according to organ involved ,), basically for undergraduates and residents in pathology
Amyloidosis refers to a group of protein misfolding diseases characterized by deposition of amyloid proteins in organs and tissues. The amyloid proteins form fibrils that take on a characteristic beta-pleated sheet structure and stain red with Congo red dye. There are two main types - AL amyloidosis involves deposition of immunoglobulin light chains and is associated with plasma cell disorders like multiple myeloma. AA amyloidosis involves serum amyloid A proteins and is secondary to chronic inflammatory conditions. Amyloid deposition damages tissues by compressing cells and restricting blood flow, commonly affecting the spleen, liver and kidneys. This can lead to organ failure and death if the underlying cause is not resolved.
The document discusses Stella Maris, LLC and mitochondrial damage diseases (MDDs) like ME/CFS, autism and Alzheimer's disease. It states that these diseases share mitochondrial dysfunction, oxidative stress, genetic factors and irregularities in metabolic processes like methylation. Common symptoms and deficiencies are also listed. Stella Maris aims to address nutritional needs of people with MDDs. Cellular respiration, methylation pathways and possible environmental causes of increased MDD prevalence are described.
Amyloidosis is a condition caused by abnormal protein deposits forming fibrils that damage tissues. These fibrils result from improperly folded proteins aggregating. There are different types depending on the precursor protein, including AL amyloidosis associated with plasma cell disorders and AA amyloidosis linked to chronic inflammation. Amyloid fibrils have a characteristic beta-pleated sheet structure and stain apple-green under polarized light when bound to Congo red dye. The deposits can affect many organs and cause tissue destruction and organ dysfunction. The kidneys, liver, spleen, heart and nervous system are commonly involved.
Amyloidosis is caused by abnormal protein deposits in tissues and organs. There are two main types of amyloid proteins that comprise amyloid deposits: fibril proteins (95%) and non-fibrillar components (5%). Amyloidosis can be systemic, affecting multiple organs, or localized affecting one or two sites. Diagnosis involves biopsy of affected tissues to identify the type of amyloid protein involved. Treatment seeks to suppress amyloid protein development and depends on the type and extent of amyloidosis.
The document discusses amyloidosis of the kidney, including its morphological characteristics, outcomes, and complications. It describes the types and classifications of amyloidosis, the microscopic and macroscopic appearance of amyloid deposits in the kidney, the development stages of renal amyloidosis from latent to nephrotic to uremic, and common complications such as infections. The document contains a detailed plan and sections on the introduction, characteristics, development, complications, and microscopic/macroscopic descriptions of renal amyloidosis.
This document provides an overview of amyloidosis, including:
- Amyloidosis is characterized by extracellular deposition of misfolded proteins that form insoluble fibrils, damaging tissues.
- There are different types classified by the misfolded protein involved, including AL, AA, and rare forms.
- Organs commonly affected include the kidney, heart, GI tract, and nerves.
- Diagnosis involves biopsy of affected tissues and staining with Congo red to identify amyloid deposits.
- Prognosis depends on type and organ involvement, with generalized amyloidosis having a poor prognosis of around 2 years.
This document summarizes key information about Alzheimer's disease (AD), including warning signs, diagnosis, causes, and potential treatments. It notes that AD is typically diagnosed through cognitive tests and ruling out other causes. Brain imaging and spinal fluid tests can help distinguish AD from other dementias. The causes of AD are not fully known but likely involve the abnormal buildup of proteins like amyloid-β and tau in the brain. Current treatments can only temporarily slow cognitive decline. Preventing and reversing AD remains very challenging due to its complex and multifactorial nature.
Hurler Syndrome is a rare genetic disorder caused by the absence of an enzyme that breaks down complex sugars, causing them to build up in the lysosome and produce severe symptoms. Sidney Van Hook, a three-year-old with Hurler Syndrome, received a bone marrow transplant which was successful but she still has some symptoms. New medications like Aldurazyme can replace the missing enzyme to stop sugar buildup and bone marrow transplants or gene therapy may help treat the disease.
The document summarizes Marfan syndrome, a genetic disorder that affects connective tissue. It is caused by mutations in the FBN1 gene and is inherited in an autosomal dominant pattern. Symptoms can include issues with the eyes, skeleton and cardiovascular system. Diagnosis is based on criteria from the 2010 Ghent revision and involves assessment of features like aortic root size and lens displacement. Untreated, it can lead to life-threatening complications such as aortic aneurysm or dissection.
Ehlers-Danlos syndrome (EDS) is a connective tissue disease caused by mutations in collagen genes. It affects connective tissues supporting skin, blood vessels, and organs. There are six main types classified by symptoms. EDS causes loose, elastic skin and fragile tissues, resulting in easy bruising and joint dislocations. While prevalence is estimated at 1 in 5,000, many cases may be undiagnosed. Treatment focuses on pain management, physical therapy, and managing complications.
Cancer is not a single disease, but rather many diseases where abnormal cells grow uncontrollably. There are over 100 types of cancer that can develop when cells in any part of the body start growing out of control. Risk factors for cancer include behaviors such as smoking, excessive alcohol consumption, poor diet, obesity, and lack of exercise. Early detection of cancer symptoms can help improve outcomes, as some cancers are curable if caught early. Leukemia is a type of cancer that affects the bone marrow and blood cells, crowding out normal cells and impairing the immune system. There are four main types of leukemia - acute, chronic, lymphocytic, and myelogenous - which differ in their rate of progression.
The document discusses amyloidosis, a group of disorders involving the deposition of abnormal proteins outside cells. There are different types including primary, secondary, systemic, localized, and hereditary amyloidosis. Secondary amyloidosis is the most common type and is caused by chronic inflammation. Clinically, amyloidosis can lead to organ enlargement and failure of the liver, kidneys, brain, and heart. Under the microscope, amyloid deposits appear as extracellular pink proteins that stain positive with Congo red and appear apple green under polarized microscopy.
Aubrey de Grey's Slide - Nigeria ICT Fest 2015nigeriaictfest
Top British gerontologist, Chief Science Officer, SENS research foundation and fellow at the Institute for Ethics and Emerging Technologies speaks about his research work on regenerative medicine at Nigeria ICT Fest 2015.
Ehlers Danlos Syndrome (EDS) is a genetic connective tissue disorder caused by defects in collagen. There are several types of EDS with varying symptoms. The hypermobility type involves loose joints and double-jointedness. Classical EDS affects the skin, causing easy bruising and scarring. The vascular type is the most severe and life-threatening due to risk of organ and blood vessel rupture. While there is no cure for EDS, physical therapy can help strengthen joints to prevent dislocation. Gene therapy may help EDS in the future by replacing or inactivating mutated genes.
Aubrey de grey why you're helpless now but not for longSelf Spark
This document discusses aging and age-related diseases. It notes that while infectious diseases have been prevented through sanitation, vaccines, antibiotics, and carrier control, age-related diseases have not. It describes aging as the lifelong accumulation of damage to tissues, cells, and molecules in the body from normal metabolic processes. This damage cannot be automatically reversed by the body and leads to disease and disability when too much damage accumulates. The document advocates for a maintenance approach to treating aging by repairing and preventing further damage as a way to significantly extend healthy lifespans. It provides examples of research into specific maintenance therapies and argues this approach could eliminate most age-related diseases.
Amyloidosis in head and neck manifestationYu-Fu Wu
This document summarizes amyloidosis, a condition characterized by extracellular deposition of fibrillary proteins. Amyloidosis can occur systemically or locally in organs. The deposition forms beta-sheet rich fibrils that take up Congo red dye, appearing apple-green under microscopy. Normally misfolded proteins are degraded, but in amyloidosis these quality control mechanisms fail, allowing accumulation. Systemic types include AL amyloidosis associated with multiple myeloma and AA amyloidosis in chronic infections/inflammation. Localized amyloidosis can affect the larynx in rare cases, presenting as slowly progressive dysphonia from diffuse thickening or discrete lesions.
This document discusses amyloidosis, which is the extracellular deposition of abnormal protein fibrils called amyloid in tissues and organs. Amyloidosis can be primary, meaning the deposition is in the disease itself, or secondary, as a complication of another underlying disease. Diagnosis involves biopsy and staining of tissues with Congo red dye to detect amyloid deposits. The kidney is a commonly affected organ where amyloid deposits are seen in the glomerular capillary tuft and surrounding tissues, which can lead to atrophy and impaired function.
This document provides an overview of amyloidosis, including:
- Amyloidosis is caused by the extracellular deposition of misfolded proteins forming fibrils. There are different types classified by the precursor protein involved.
- Systemic forms include AL amyloidosis associated with plasma cell disorders and AA amyloidosis associated with inflammatory conditions.
- Diagnosis involves biopsy of tissues like fat pad or organs stained with Congo red to identify amyloid deposits. Immunohistochemistry identifies the precursor protein type.
- Organ involvement varies but kidney, heart, liver and spleen are commonly affected. Clinical manifestations depend on the organs involved and may include proteinuria, heart failure, hepatomegaly or neurological symptoms.
This is a series of notes on general pathology.. Amyloidosis is a very important topic from exam point of view both for under and post graduates..topic is presented here with enough colour illustrations
Amyloidosis comprises a group of diseases characterized by the extracellular deposition of insoluble fibrous amyloid proteins in various body tissues. There are at least 20 different types of amyloid proteins that can form fibrils and deposit in tissues. The classification of amyloidosis has evolved from descriptive terms to designations based on the type of amyloid fibril protein involved (such as AL, AA, and TTR amyloidosis). AA amyloidosis is caused by deposition of amyloid A protein and is associated with long-term inflammatory conditions like familial Mediterranean fever. It commonly involves the kidneys and gastrointestinal tract and can lead to renal failure. Treatment focuses on managing the underlying inflammatory condition to reduce amyloid A protein levels and prevent further deposition.
amyloidosis(including history,physical and chemical properties, classification, variants, staining characteristics, lab diagnosis,morphological patterns according to organ involved ,), basically for undergraduates and residents in pathology
Amyloidosis refers to a group of protein misfolding diseases characterized by deposition of amyloid proteins in organs and tissues. The amyloid proteins form fibrils that take on a characteristic beta-pleated sheet structure and stain red with Congo red dye. There are two main types - AL amyloidosis involves deposition of immunoglobulin light chains and is associated with plasma cell disorders like multiple myeloma. AA amyloidosis involves serum amyloid A proteins and is secondary to chronic inflammatory conditions. Amyloid deposition damages tissues by compressing cells and restricting blood flow, commonly affecting the spleen, liver and kidneys. This can lead to organ failure and death if the underlying cause is not resolved.
The document discusses Stella Maris, LLC and mitochondrial damage diseases (MDDs) like ME/CFS, autism and Alzheimer's disease. It states that these diseases share mitochondrial dysfunction, oxidative stress, genetic factors and irregularities in metabolic processes like methylation. Common symptoms and deficiencies are also listed. Stella Maris aims to address nutritional needs of people with MDDs. Cellular respiration, methylation pathways and possible environmental causes of increased MDD prevalence are described.
Amyloidosis is a condition caused by abnormal protein deposits forming fibrils that damage tissues. These fibrils result from improperly folded proteins aggregating. There are different types depending on the precursor protein, including AL amyloidosis associated with plasma cell disorders and AA amyloidosis linked to chronic inflammation. Amyloid fibrils have a characteristic beta-pleated sheet structure and stain apple-green under polarized light when bound to Congo red dye. The deposits can affect many organs and cause tissue destruction and organ dysfunction. The kidneys, liver, spleen, heart and nervous system are commonly involved.
Amyloidosis is caused by abnormal protein deposits in tissues and organs. There are two main types of amyloid proteins that comprise amyloid deposits: fibril proteins (95%) and non-fibrillar components (5%). Amyloidosis can be systemic, affecting multiple organs, or localized affecting one or two sites. Diagnosis involves biopsy of affected tissues to identify the type of amyloid protein involved. Treatment seeks to suppress amyloid protein development and depends on the type and extent of amyloidosis.
The document discusses amyloidosis of the kidney, including its morphological characteristics, outcomes, and complications. It describes the types and classifications of amyloidosis, the microscopic and macroscopic appearance of amyloid deposits in the kidney, the development stages of renal amyloidosis from latent to nephrotic to uremic, and common complications such as infections. The document contains a detailed plan and sections on the introduction, characteristics, development, complications, and microscopic/macroscopic descriptions of renal amyloidosis.
This document provides an overview of amyloidosis, including:
- Amyloidosis is characterized by extracellular deposition of misfolded proteins that form insoluble fibrils, damaging tissues.
- There are different types classified by the misfolded protein involved, including AL, AA, and rare forms.
- Organs commonly affected include the kidney, heart, GI tract, and nerves.
- Diagnosis involves biopsy of affected tissues and staining with Congo red to identify amyloid deposits.
- Prognosis depends on type and organ involvement, with generalized amyloidosis having a poor prognosis of around 2 years.
This document summarizes key information about Alzheimer's disease (AD), including warning signs, diagnosis, causes, and potential treatments. It notes that AD is typically diagnosed through cognitive tests and ruling out other causes. Brain imaging and spinal fluid tests can help distinguish AD from other dementias. The causes of AD are not fully known but likely involve the abnormal buildup of proteins like amyloid-β and tau in the brain. Current treatments can only temporarily slow cognitive decline. Preventing and reversing AD remains very challenging due to its complex and multifactorial nature.
Cellular Energy: Mechanisms, Importance, and Regulation | The Lifesciences Ma...The Lifesciences Magazine
Every living thing is powered by cellular energy, which powers the molecular reactions necessary for survival. Numerous organelles and routes are part of this complex system, with the mitochondria frequently being thought of as the cell's powerhouse.
1. Amyloidosis occurs when misfolded proteins aggregate into insoluble fibrils that deposit in tissues, damaging organ structure and function.
2. There are different types of amyloidosis depending on the type of protein that aggregates, including light chain (AL), amyloid A (AA), and variants associated with specific proteins like transthyretin.
3. Amyloidosis can be localized to single organs or systemic, and systemic forms include primary amyloidosis associated with plasma cell disorders, secondary amyloidosis linked to chronic inflammation, and rare hereditary types.
Amyloidosis is a group of diseases characterized by abnormal protein deposits in tissues called amyloid. There are different types depending on the protein involved, including AL amyloid from plasma cells and AA amyloid from inflammatory conditions. The deposits disrupt tissue structure and function. The disease is diagnosed through biopsy showing amyloid's green birefringence with Congo red staining. Treatment focuses on the underlying cause when possible to stop further amyloid accumulation.
- Amyloidosis is a group of diseases where an abnormal protein builds up in tissues and organs. This protein forms fibrils that disrupt normal function.
- The most common types are AL amyloidosis associated with plasma cell disorders and AA amyloidosis which occurs due to chronic inflammation.
- Symptoms depend on the organs affected but often involve the kidneys, heart, liver, and GI tract. Biopsy of affected tissues showing amyloid deposits under Congo red staining is required for diagnosis.
Gene dosage refers to the number of copies of a gene present. Changes in gene dosage can affect the amount of gene product expressed and cause phenotypic consequences. Collagen is the main structural protein in connective tissue and comes in many types, with Type I being over 90% of the human body's collagen. Gene defects in collagen genes like COL1A1 and COL2A1 can cause disorders like osteogenesis imperfecta and Alport syndrome. Osteogenesis imperfecta is caused by defects in type I collagen production and results in brittle bones. It has varying severity from mild to lethal. Treatment focuses on preventing fractures and improving quality of life. The PMP22 gene codes for a myelin protein, and imbalances in
Geriatrics is a subspecialty of internal medicine that focuses on healthcare for elderly people. It aims to promote health and prevent/treat diseases and disabilities in older adults. Some key theories of aging include programmed senescence (cells have a limited number of divisions), endocrine/hormonal changes, immunological changes, wear and tear, and error catastrophe. Geriatric syndromes that commonly affect older adults include disability, dementia, falls, polypharmacy, pressure ulcers, and urinary incontinence. Dementia is a syndrome involving cognitive decline and can be caused by conditions like Alzheimer's, strokes, infections, and substance abuse. Falls are a leading cause of injury for older adults and risk factors include age
Geriatrics is a subspecialty of internal medicine that focuses on healthcare for elderly people. It aims to promote health and prevent/treat diseases and disabilities in older adults. The term comes from Greek words meaning "old man" and "healer". Geriatrics addresses common geriatric syndromes like disability, dementia, falls, polypharmacy, pressure ulcers, and urinary incontinence. Dementia is a syndrome involving cognitive decline and can have many causes like Alzheimer's disease. It is a growing problem worldwide due to the aging population. Falls are also common in older adults and a leading cause of injury, with risk factors like age, medications, vision problems and muscle weakness. Polypharmacy, taking multiple
Amyloidosis is a group of diseases caused by abnormal protein deposits in tissues. There are different types of amyloid proteins that can deposit, including immunoglobulin light chains (AL), serum amyloid A (AA), and beta-amyloid. The deposits disrupt organ function over time and can affect the kidneys, heart, liver, spleen, and tongue. Symptoms vary by the organs involved but may include kidney failure, heart failure, digestive issues, and enlarged tongue. The prognosis depends on the type and extent of amyloidosis. Treatment focuses on managing the underlying condition that causes protein deposition or targeting the amyloid deposits directly.
Alzheimer's disease is a progressive condition, which means the symptoms develop gradually over many years and eventually become more severe. It affects multiple brain functions.
The first sign of Alzheimer's disease is usually minor memory problems.
For example, this could be forgetting about recent conversations or events, and forgetting the names of places and objects.
As the condition develops, memory problems become more severe and further symptoms can develop, such as:
confusion, disorientation and getting lost in familiar places
difficulty planning or making decisions
problems with speech and language
problems moving around without assistance or performing self-care tasks
personality changes, such as becoming aggressive, demanding and suspicious of others
hallucinations (seeing or hearing things that are not there) and delusions (believing things that are untrue)
low mood or anxiety
This document outlines amyloidosis, a disease characterized by abnormal protein deposits in tissues. Amyloidosis has several subtypes depending on the type of misfolded protein involved. The deposits have characteristic staining properties including apple-green birefringence under polarized light when stained with Congo red. Clinically, amyloidosis can affect many organs, with kidney, heart and liver among the most commonly involved. Deposits in organs like kidney can lead to nephrotic syndrome and renal failure. The prognosis depends on the extent and location of protein deposits in the body.
Alzheimer's is a brain disease that causes degeneration of brain cells. It affects around 4 million people in the US and is predicted to affect over 1 in 85 people globally by 2050. Alzheimer's causes memory loss, confusion, and difficulty performing daily tasks. While age is the greatest risk factor, family history and genetics may also play a role. Currently, there is no cure and treatment aims to slow the progression of symptoms. Future research focuses on earlier diagnosis and discovering preventative measures to reduce risk.
Autoimmune disease HEMOLYTIC ANEMIA AND DIABETESArchanaSoni3
An autoimmune disease is a condition in which your immune system mistakenly attacks your body.
The immune system normally guards against germs like bacteria and viruses. When it senses these foreign invaders, it sends out an army of fighter cells to attack them.
Normally, the immune system can tell the difference between foreign cells and your own cells.
In an autoimmune disease, the immune system mistakes part of your body — like your joints or skin — as foreign. It releases proteins called autoantibodies that attack healthy cells.
Some autoimmune diseases target only one organ. Type 1 diabetes damages the pancreas. Other diseases, like lupus, affect the whole body.
Styles of Scientific Reasoning, Scientific Practices and Argument in Science ...Elsa von Licy
The document discusses various topics related to scientific reasoning, practices, and argumentation including different styles of scientific thinking, features of scientific knowledge, and teaching and learning science. It provides examples of "crazy ideas" in science that are now accepted, examines the role of argument in science, and outlines the scientific practices and central questions of science. It also discusses developing models, planning investigations, analyzing data, and constructing explanations as key scientific practices.
Anti-philosophy rejects traditional philosophy and logic, instead embracing creativity, spirituality, and personality. It considers philosophy to be dead, kept alive artificially by analytic philosophers. The document criticizes how philosophy is currently taught and argues it has become unproductive, replacing original aims with nonsense. Anti-philosophy's goal is not to destroy philosophy but to transform its current state and avoid fundamentalism in philosophy and science.
There is no_such_thing_as_a_social_science_introElsa von Licy
This document provides an introduction and overview of the arguments made in the book "There is No Such Thing as Social Science". It begins by stating the provocative title and questioning whether the authors will take it back or qualify their position.
It then outlines three ways the term "social science" could be used - referring to a scientific spirit of inquiry, a shared scientific method, or reducibility to natural sciences. The authors argue against the latter two, methodological and substantive reductionism.
The introduction discusses how opponents may accuse the authors of being a priori or anti-reductionist, but argues that those defending social science are actually being dogmatic by insisting it must follow a scientific model. It frames the debate as being
3. 1. One Minute Overview
2. WHAT IS AMYLOIDOSIS?
All of the normal proteins in our body are biodegradable
and recyclable. Amyloidosis is a disease in which abnormal proteins (amyloid) are resistant to being broken down.
As a consequence, the amyloid proteins deposit and accumulate in the body’s tissues. If amyloid builds up in the
kidney, heart, liver, gastrointestinal tract or nerves, it causes
those organs to function poorly. Thus, the symptoms of
amyloidosis are associated with the abnormal functioning
of the organs involved. Typically, patients will have some of
the following symptoms: unexplained weight loss, fatigue,
shortness of breath, foamy urine, swelling in the ankles and
legs, as well as numbness and tingling in the hands and
feet. These are manifestations of damage to the underlying
organs from the insoluble amyloid protein. Treatments are
designed either to dissolve the amyloid deposits or to interrupt their production. Left untreated, the disease can be
life-threatening. Therefore, early and accurate diagnosis is
the key to promoting positive outcomes.
Throughout our lifetime, our DNA is coding for the manufacture of small molecules called proteins. These proteins provide
the structure and function for nearly all of life’s biological processes. Enzymes that facilitate our cells’ chemistry, hormones
that affect our body’s growth and regulation, and antibodies
that form our immune response are all examples of proteins in
action. Just about everything in our bodies – from the color of
our eyes, to carrying oxygen in our blood, to whether we can
digest milk – is determined by the proteins we make.
1
Once produced within the body, proteins will naturally fold
into a particular shape. This natural form of a protein molecule is what allows for its specific function. Put simply,
when proteins are folded properly, they work as they should,
and we enjoy relatively good health. When proteins are misfolded, it affects our body’s ability to function, and problems
may arise over time.
Misfolded proteins can be produced because of genetic
causes, or because of other factors related to chronic inflammation or increasing age. Regardless, our bodies are
usually capable of identifying and removing these abnormal
proteins. In some cases, though, we either produce too
much of the abnormal proteins for our body to handle, or we
are not able to break down and clean up the proteins at all.
Such defects in protein production and processing are associated with many diseases.
What is Amyloidosis?
2
4. Broadly speaking, amyloidosis (pronounced ‘am-uh-loydoh-sis’) is one class in a growing list of protein folding disorders. While there are many distinct types of amyloidosis,
in all cases the misfolded proteins, called amyloid (meaning
‘starch-like’), take on a particular shape that makes it difficult for the body to break down. Because of this misfolding,
the amyloid proteins bind together to form rigid, linear fibers
(or fibrils) that accumulate in our body’s organs and tissues.
Depending on where the amyloid builds up, such as in the
kidney, heart and nerves, different symptoms and potentially
life-threatening conditions become manifest.
While amyloidosis has been known since the 19th century, it
is only within the last few decades that our understanding of
it has matured. Presently, there are over 25 different proteins
that have been identified as contributing to amyloidosis (the
major forms of which are described in the next section). Additional types of precursor proteins that can lead to amyloid
formation continue to be discovered through ongoing research.
Amyloid is a starch-like substance caused by the misfolding of proteins.
Amyloid binds together into rigid, linear fibers (fibrils) that deposit in the
tissues and organs.
3
Certainly, amyloidosis is a rare condition and often overlooked. Each year, an estimated 50,000 people worldwide
will become afflicted with the disease, with more than 3,000
people being diagnosed in North America alone. This is
about 1/5 of the incidence of multiple myeloma, and of
similar incidence to that of Hodgkin’s disease or chronic myelogenous leukemia. Because of its rarity, medical students
What is Amyloidosis?
4
5. and physicians may not expect to see amyloidosis in their
practice. Moreover, because the condition’s nonspecific,
ever-worsening symptoms (e.g., being tired or out of breath)
may be mistaken for more common problems of lung and
cardiovascular disease, it is very likely that the actual prevalence of amyloidosis is greater than now recognized.
It is imperative for clinicians and pathologists to consider
amyloidosis as part of their differential diagnosis (discussed
in section 4). Given the unique staining and spectroscopic
properties of amyloid proteins, it is a simple matter to test
for the disease. Early, accurate diagnosis is essential for patients to benefit from new treatments (discussed in section
5) that are available to improve and extend life.
Misfolded proteins can be produced because of genetic causes, or
because of other factors related to chronic inflammation or increasing
age.
5
What is Amyloidosis?
6
6. 3. TYPES OF AMYLOIDOSIS
There are many different proteins in our bodies that can become misfolded to produce amyloidosis. The predisposition
to form abnormal proteins can be inherited from our parents, or even arise from DNA mutations acquired during our
lifetime. In some instances, amyloidosis results from chronic
inflammatory and infectious diseases, or long-term kidney
dialysis. Most diagnosed cases, however, are caused by a
bone marrow condition that has similarities with multiple
myeloma.
As the amyloid proteins accumulate in our bloodstream,
they ultimately deposit in organs and tissues. The resulting
amyloid fibrils may impair multiple organ systems or localize in one area of the body. Amyloid will deposit most commonly in the kidney, heart and nerves, with the liver, spleen,
gastrointestinal tract, and airways also occasionally affected. Amyloid is oftentimes found in the pancreas of people
who develop diabetes as adults.
Although the precursor proteins that lead to amyloidosis
come in various shapes and sizes, they all share the same
misfolded structure as amyloid deposits. This unifying
feature of amyloid, wherein a protein’s normal alpha-helical
shape misfolds into a beta-pleated sheet, allows for precise
and timely diagnosis of the disease (discussed in the next
section).
7
While the condition’s symptoms and treatments depend on
the organs affected, the several types of amyloidosis can
be classified according to the precursor protein involved. As
seen in Table 1 (next page), a convenient naming system is
used, such that the prefix “A” refers to amyloid, followed by
an abbreviation for the associated protein. For example, AL
designates amyloid derived from light-chain antibodies; AA
designates serum amyloid A protein; and ATTR designates
amyloid from transthyretin.
As new amyloid proteins are characterized, and as our
medical understanding deepens, it is possible to discuss the
different types of amyloidosis from a wider perspective. Below is a brief description of AL amyloidosis; AA amyloidosis;
familial amyloidosis; senile systemic amyloidosis; as well as
ALECT2, dialysis-related, and localized amyloidosis.
AL Amyloidosis
AL (or primary) amyloidosis is the most commonly diagnosed form of the disease, accounting for 85% of all cases
in developed countries. The disorder begins in the bone
marrow, the soft tissue that fills the cavities of our bones,
where red and white blood cells are formed. One kind of
white blood cell, called plasma cells, produces antibodies
that protect us from infections. These antibody proteins (immunoglobulins) are made up of light and heavy chain mol-
Types of Amyloidosis
8
7. TYPE
SOURCE OF AMYLOID
(Precursor Protein)
SYNDROME
AL, AH,
ALH
Plasma cells in the
bone marrow
(Immunoglobulin light
or heavy chains, or both)
Primary form of amyloidosis, similar to
multiple myeloma, affecting the
kidneys, heart, liver, gastrointestinal
tract, and nerves.
AA
Circulating
inflammatory protein
(Serum amyloid A)
Secondary to chronic inflammatory
and infectious diseases, affecting the
kidneys and liver.
ALECT2
White blood cells
(Leukocyte
chemotactic factor 2)
Clinically resembles AL, affecting the
kidneys and liver.
Aβ2M
Circulating serum protein
( β2-microglobulin)
ATTR
Mutant and wild-type
protein produced
in the liver
(Transthyretin)
Dialysis-related, affecting the joints
and tendons.
Hereditary with over 100 mutations,
affecting the nervous system, heart,
and kidneys. The Val-122-Ile muta tion is common in African Americans,
causing cardiac disease. A nonhereditary, wild-type, senile form
causes cardiac disease in the elderly.
AFib
Mutant protein
produced in the liver
(Fibrinogen A α-chain)
AApoAI
Circulating serum protein
(Apolipoprotein AI)
Hereditary, affecting the liver, heart,
kidneys, and nerves.
ALys
Circulating serum protein
(Lysozyme)
Hereditary, affecting the gastrointesti nal tract and kidneys.
AGel
Circulating serum protein
(Gelsolin)
Hereditary, affecting the skin, nerves,
and kidneys.
Localized
Plasma cells in
local tissues
(Immunoglobulin
light chains)
Hereditary, affecting the kidneys.
ecules. Normally, our plasma cells produce whole antibodies, and our body breaks down these proteins and recycles
them after a short time. In AL, though, too many unassembled, misfolded light chains are being made. These “free
light chains” (and, in rare cases, free heavy chains) cannot
be broken down efficiently. They bind together to form amyloid fibrils that build up in the extracellular space of organs
and tissues. In this way, the body’s normal functioning is
impaired. Problems typically arise in the kidney, heart, liver,
spleen, nerves, intestines, skin, tongue, and blood vessels.
AA Amyloidosis
AA (or secondary) amyloidosis results from increased levels
of the circulating serum amyloid A protein. Serum amyloid
A elevates in our blood as a natural response to infection
and inflammation. In general, if a patient has an infection or
inflammatory condition for six months or more, he or she is
at risk for developing AA. The amyloidosis arises secondary
to chronic inflammatory and infectious conditions, including:
rheumatic disease, inflammatory bowel disease, tuberculosis, osteomyelitis, lupus, and hereditary fever syndromes
such as familial Mediterranean fever. Amyloid deposition
usually begins in the kidneys, but the liver, spleen, lymph
nodes, and intestines are also commonly affected.
Mostly occurs in the bladder, skin,
and airways.
Table 1: Examples of amyloidosis. The naming system combines an “A”
for amyloid with an abbreviation for the protein underlying the condition.
Types of Amyloidosis
10
8. Familial Amyloidosis
Familial (or hereditary) amyloidosis, as the name implies, is a
heritable form of the disease. Whether a mutation has occurred in one’s own DNA, or was inherited from one’s parents, the most common form of familial amyloidosis is associated with a mutant transthyretin (TTR) protein produced
in the liver. TTR is a protein that helps to transport thyroxine
(a thyroid hormone) and retinol (vitamin A) around the body.
There are over 100 known mutations of TTR that cause the
protein to become unstable and misfold into amyloid. Various organs are affected, especially the nervous system
and heart, with symptoms occurring in mid- to late life. If
the nerves are primarily affected, the condition is known as
familial amyloid polyneuropathy; if the heart is primarily affected, it is known as familial amyloid cardiomyopathy.
The most common known mutation of TTR is called Val-30Met, causing nerve damage and electrical problems with the
heart. Another common mutation in the United States is Thr60-Ala which causes thickening of the heart muscle. While
transthyretin-mediated amyloidosis (ATTR) occurs in families
of nearly every ethnicity, there is one TTR variant, Val-122Ile, that appears to be common in the African-American
population. It is estimated that 4% of African Americans
carry this mutant gene, comprising upwards of 25% of
African American patients with amyloidosis. This mutation
may be an often unrecognized cause of cardiac disease in
African Americans.
11
In addition to ATTR, there are other gene mutations for different proteins that lead to amyloidosis. Though very rare,
some of these include: AFib (from fibrinogen A α-chain);
AApoAI (from apolipoprotein AI); ALys (from lysozyme); and
AGel (from gelsolin).
Senile Systemic Amyloidosis
Senile systemic (or age-related) amyloidosis is a late onset
disease that is acquired, not inherited. Amyloid deposits
accumulate in the body from normal (wild-type) proteins.
The best known example of senile systemic amyloidosis
arises from the buildup of wild-type transthyretin (TTR) in the
hearts of the elderly. Unlike familial amyloidosis, there are
no mutations of the TTR gene, but the slowly progressive
cardiac disease has similar symptoms. Whether mutant or
wild-type, TTR-mediated amyloidosis is thought to be more
common than AL amyloidosis, though it often goes undiagnosed. For example, wild-type TTR is found in up to 30% of
patients showing clinical “heart failure with preserved ejection fraction.”
Other examples of senile amyloidosis include: APro (from
prolactin); ACal (from calcitonin); AIAPP (from amylin); and
AANF (from atrial natriuretic factor). All are derived from the
misfolding of wild-type proteins. Despite its name, this condition has no relationship to senility or dementia.
Types of Amyloidosis
12
9. In AL amyloidosis, plasma cells in the bone marrow produce too many
“free light chain” antibodies. These proteins misfold into amyloid,
accumulate in the blood, and deposit in many organ systems.
ALECT2 Amyloidosis
One of the most recent additions to the class of amyloid
proteins is ALECT2, derived from a protein made by white
blood cells (leukocytes). As part of ongoing research, it has
13
yet to be determined whether ALECT2 is the result of genetic mutations; however, the effect of the disease closely
resembles that of AL, often affecting the kidneys. Because
Types of Amyloidosis
14
10. amyloid deposits can result from normal (wild-type) proteins,
as with senile systemic amyloidosis, this form of the disease
may be mis- or underdiagnosed. One study, in fact, suggested that ALECT2 was the most common, undiagnosed
type of amyloid, especially among patients of Mexican heritage. In an analysis of amyloid-containing kidney specimens
over the last 8 years, ALECT2 was the third most common
type (2.5%), as compared to AL (86%), AA (7%) and ATTR
(1.4%).
Aβ2M Amyloidosis
Aβ2M (or dialysis-related) amyloidosis often occurs in patients suffering from kidney failure who have been on dialysis for many years. A circulating serum protein, beta-2
microglobulin (β2M), accumulates in the blood because it
is unable to cross through the dialysis filter. Because β2M
cannot be excreted from the body, the resulting amyloid
builds up in tissues, particularly in the joints and tendons.
This causes pain, stiffness and fluid in the joints, as well as
carpal tunnel syndrome.
or lungs). Deposits have also been diagnosed in the eye,
gastrointestinal tract, skin, and breast. Similar to AL amyloidosis, the localized amyloid deposits are made up of light
chain proteins. However, in localized amyloidosis, the abnormal plasma cells producing the amyloid light chains are
in the affected tissues, not in the bone marrow.
Other non-systemic types of amyloidosis are associated
with hormone proteins, aging, or specific areas of the body.
One special case of localized amyloidosis is cerebral amyloid angiopathy (CAA). While the cause is still unknown, in
some individuals CAA may be hereditary. Amyloid protein
deposits in the walls of the brain’s arteries, increasing the
risk of stroke and dementia. This neurological condition is
mostly seen in older patients, and it is unrelated to Alzheimer’s disease.
Localized Amyloidosis
Though the major forms of amyloidosis are described
above, it is important to recognize that amyloid deposits
may occasionally occur in isolated areas without evidence
of a systemic disease. These localized, tumor-like deposits
most often occur in the bladder and airways (e.g., trachea
15
Types of Amyloidosis
16
11. 4. DIAGNOSIS
In some sense, amyloidosis is not easy to recognize. Its
symptoms are vague and nonspecific, often mimicking those
of other common conditions. For instance, shortness of
breath can be an indicator of heart disease, which is usually
caused by atherosclerosis and coronary artery disease. One
would not initially think of amyloidosis. Also, protein in the
urine is an early sign of kidney disease, as in patients with diabetes, but again, one does not normally think of amyloidosis.
Amyloidosis typically appears in middle-age and older
individuals, but it can also occur during one’s 30s or 40s,
and occasionally even younger. Amyloid deposits can cause
weight loss, fatigue, shortness of breath, dizziness upon
standing, swelling in the ankles and legs, numbness and
tingling in the hands and feet, foamy urine, alternating bouts
of constipation and diarrhea, and feeling full quickly after
eating. Also, if a patient bruises easily, especially around the
eyes (periorbital purpura), or has an enlarged tongue (macroglossia), amyloidosis is very likely the underlying cause.
As a constellation of symptoms persists and worsens, many
physicians do not consider (or remember) to look for such a
rare, insidious disease. It is not uncommon for an individual
to see several physicians before a biopsy (tissue sample) is
taken, or to develop organ failure before a proper diagnosis
17
Symptoms are often vague, mimicking those of other common conditions. Therefore, a multidisciplinary approach among physician specialists
is essential for diagnosis. In some cases, telltale signs of amyloidosis are
an enlarged tongue (macroglossia) or bruising around the eyes (periorbital
purpura).
is made. Indeed, if pathologists are waiting for clinical information to look for amyloidosis, they will miss the majority of
cases.
While amyloidosis can affect just a single organ, it often
causes systemic problems (i.e., affects more than one organ
system). The organs most often involved are the kidneys
(about 70% of patients), heart (50%), nervous system (30%),
Diagnosis
18
12. and gastrointestinal tract. Therefore, in patients with combinations of kidney, heart, nerve, gastrointestinal or liver disease
– with no obvious cause – it should prompt physicians to test
for amyloidosis.
As part of the differential diagnosis (i.e., the process of distinguishing one disease from another), the four most common
clinical settings in which amyloidosis should be considered are:
1. Loss of massive amounts of protein in the urine (proteinuria)
2. Stiff or thickened heart (restrictive cardiomyopathy) as
seen on echocardiogram; low voltage seen on electrocardiogram; irregular heartbeat (arrhythmia) that is resistant
to conventional treatment, often associated with normal or
low blood pressure; or unexplained heart failure
3. Enlarged liver (hepatomegaly) without alcohol consumption
or other explanation, often with abnormal liver blood tests
4. Numbness or pain in the fingers or toes (peripheral neuropathy), such as carpal tunnel syndrome, or alternating
bouts of constipation and diarrhea (autonomic neuropathy), while also feeling light-headed (low blood pressure)
when standing up.
Testing for Amyloidosis
Once amyloidosis is suspected, it can usually be identified, if
present, with a very simple office procedure. Early detection
and accurate evaluation are essential for patients to benefit
from the many therapies now available (discussed in the next
section).
19
Blood and urine tests may reveal an abnormal protein in the
body, but the gold standard for detecting amyloid deposits
is to employ Congo red staining on a tissue sample. Biopsies can be taken from the gums, nerves, kidney, liver, or
rectum. However, the easiest way to get a tissue sample is
to aspirate fat from the abdomen. In this non-invasive procedure, the skin of the belly is numbed with a local anesthetic, and a needle is used to perform a mini-liposuction
of fat cells from under the skin. Because of the common
misfolded structure of all amyloid, it has a pink color when
dyed with Congo red in the laboratory, and a characteristic
apple-green birefringence when viewed with a polarizing
microscope. This signature technique is able to diagnose
amyloidosis in 70-80% of patients.
If the fat pad aspirate is negative for amyloidosis, but suspicion of the disease is high, a direct biopsy of the involved
organ (e.g., the heart, kidney, or liver) should be done. If
amyloid is present, the use of Congo red staining will yield a
definitive diagnosis in nearly 100% of cases.
Immunohistochemistry must be performed and interpreted
with caution. It is important to avoid over-staining the tissue sample with Congo red, as this may give false results.
Visualizing the tissue with an electron microscope will
show the classic structure of amyloid fibrils, thus confirming its presence.
Diagnosis
20
13. Typing the Amyloidosis
Whether amyloid is found in the tissue biopsy or the results
are inconclusive, it is recommended to contact specialized
amyloidosis centers (see section 6) using more sophisticated
methods. Proving that amyloid is present in an organ is only
the beginning of the process. Now it must be determined
what kind of amyloid is causing the disease in order to plan
for an appropriate, individualized treatment.
In all cases, identifying the amyloid type must be based on
evaluation of the abnormal proteins deposited in the affected tissues. A simple blood test to measure the abnormal
production of serum free light chains will show disproportionately elevated levels in roughly 98% of patients with
AL (or primary) amyloidosis. Subsequently, a bone marrow
biopsy, with appropriate immunohistochemical staining or
flow cytometry analysis, will demonstrate a clonal population of plasma cells in most patients, which are producing
the defective antibody light chains. If these tests are negative, a hereditary form of the disease should be investigated.
Molecular and genetic testing can be performed on blood
samples to see if the patient has any of the familial types of
amyloid (e.g., TTR, fibrinogen, lysozyme, apolipoproteins AI
and AII, and gelsolin). If one has such a mutation, then his or
her children will have a 50% chance of inheriting it.
The gold standard for detecting amyloidosis uses Congo red stain on a
tissue sample, which appears apple-green when viewed with a polarizing
microscope. Laser microdissection followed by mass spectrometry can
determine the type of amyloid in virtually 100% of cases.
21
It should be emphasized that the presence of a genetic
mutation does not always correlate with the type of amyloidosis. For example, a patient can have AL amyloidosis
while also carrying a genetic variant that is not the cause of
their disease. For this reason, the unequivocal identification
of the amyloid protein must be made in concert with other
diagnostic techniques. (Please note: In the United States,
Diagnosis
22
14. For patients with chronic inflammatory or infectious conditions, or long-term kidney dialysis, blood tests will suggest
the presence of AA or Aβ2M amyloidosis. If a patient is older
than 50 years and presenting with congestive heart failure,
or signs of dementia or stroke, a physician should consider
clinically isolated types of the disease such as senile systemic amyloidosis (SSA) or cerebral amyloid angiopathy
(CAA), as evidenced in echocardiograms and magnetic
resonance imaging.
Meanwhile, recent advances in the field of proteomics promise to revolutionize the precise diagnosis of amyloidosis.
Proteomics involves the study of the entire complement of
proteins in an organism or environment. Unlike standard
immunochemistry techniques, which can be limited in their
availability, specificity, and sensitivity, proteomics can identify
any protein – with or without genetic mutations – in one single
test. This provides huge time- and cost savings in accurately
identifying amyloid proteins from available tissue samples.
Thus, laser microdissection followed by mass spectrometry
(LMD-MS) is the premier technique in typing amyloidosis.
To perform the test, Congo-red positive samples are dis23
• Excessive protein in the urine (proteinuria)
• Stiff or thickened heart (restrictive cardiomyopathy)
• Enlarged liver (hepatomegaly)
• Numbness or pain in the hands or feet (peripheral neuropathy), or
alternating bouts of constipation and diarrhea (autonomic neuropathy),
in the presence of light-headedness (low blood pressure)
Abdominal fat pad aspirate or involved organ biopsy
Congo red staining
Electron microscopy
Positive birefringence
8-10 nm fibrils
Amyloidosis
Serum free light chain assay
Positive for either lambda
or kappa free light chains
+/- heavy chains
TYPING
the Genetic Information Nondiscrimination Act legislates
that patients who have a hereditary disposition for diseases,
such as amyloidosis, cannot be discriminated against with
respect to employment or health insurance.)
DIAGNOSIS
Clinical suspicion of amyloidosis, including multiple organ
involvement without an obvious cause. For example:
AL, AH or ALH
amyloidosis
Confirmation with bone
marrow biopsy, monoclonal
protein studies, and laser
microdissection with mass
spectrometry
Equivocal or
negative results
Genetic testing
and immunohistochemistry
Proteomics laser
microdissection with
mass spectrometry
Confirmation of
AA, TTR, AFib,
ALECT2, Aβ2M, etc.
Table 2: Diagnosis flowchart. A general workflow for detecting amyloidosis
and determining what type of amyloid is underlying the condition.
15. sected and broken down into smaller components of protein
molecules (called peptides). The peptides are then analyzed
using a process known as “liquid chromatography electrospray tandem mass spectrometry.” LMD-MS can be performed on any tissue samples, including a fat pad aspirate
if amyloid is present. Studies have shown that LMD-MS has
the capability to identify all known amyloid proteins with virtually 100% accuracy, as well as the ability to characterize
new ones. Regardless of a patient’s symptoms, no previous
clinical knowledge is necessary in typing the amyloidosis
with LMD-MS.
While certain forms of amyloidosis often are underdiagnosed
– such as the TTR variant, Val-122-Ile, that causes cardiac
disease in African Americans, and the wild-type ALECT2 protein that causes kidney disease in patients of Mexican heritage – with LMD-MS this no longer has to be the case.
In summary, amyloidosis affects individuals of various ages
and ethnicities, and the risk of developing the disease is
greater in people who:
• Are 50 years and older
• Have a chronic infection or inflammatory disease
• Have a family history of amyloidosis
• Have multiple myeloma (about 10% of patients with
multiple myeloma also develop amyloidosis)
• Have a kidney disease that requires dialysis for several
years.
25
5. treatments
Some physicians used to assume that nothing could be
done for a patient with amyloidosis. This is simply not true,
especially as treatments have become more effective. Eventually, as therapies continue to develop and refine, amyloidosis will be little more than a treatable nuisance.
Working with a team of physicians – including hematologists,
cardiologists, nephrologists and neurologists, among others
– it is important to get a conclusive, accurate diagnosis of the
disease as soon as possible. The treatments available depend
on the type of amyloidosis and the organs affected, as well as
on the patient’s condition, age, and personal preference. If not
treated in a timely manner, amyloid deposits will continue to
damage tissues until organ failure, and possibly death.
Treatment of amyloidosis is a two-part process: (1) Manage
symptoms to promote the patient’s well-being, quality of life,
and survival; and (2) Eliminate the supply of amyloid protein
to improve organ function.
There are three general approaches to disrupt the formation
and deposition of amyloid protein, which vary according to
the type of amyloidosis. The most common treatment interferes with the production of the precursor protein leading to
the disease. A second method uses drug therapy to stabi-
Treatments
26
16. lize the normal structure of the precursor protein, thus preventing it from misfolding into amyloid. A third strategy is to
target amyloid deposits directly, by destabilizing the amyloid
fibrils so they can no longer remain misfolded.
ing chemotherapy may have side effects such as nausea,
vomiting, hair loss, infection and extreme fatigue. If the side
effects interfere with one’s quality of life, different regimens
may be available.
All therapies have side effects, and one’s doctors will be
sure to recommend the best options. In many cases, if the
source of abnormal protein is removed, existing amyloid
deposits can be reabsorbed with time, and organ function
can be restored.
In carefully selected patients, chemotherapy is combined
with stem cell transplantation. Stem cells are found in the
bone marrow, and they develop into several kinds of blood
cells, including our plasma cells. Once the plasma cells are
destroyed using high doses of chemotherapy, the bone marrow is replenished with fresh stem cells from a patient’s own
body (autologous transplant). With eradication of the faulty
plasma cells, amyloid production is slowed or stopped, and
the bone marrow can become healthy again.
AL Amyloidosis
For AL (or primary) amyloidosis, the most commonly diagnosed form of the disease, extensive organ involvement is
usual. Without treatment, the average survival rate is about
12-18 months, and only about 6 months for patients with
severely impaired heart function.
Chemotherapy, either orally or intravenously, forms the
cornerstone of treatment for AL amyloidosis. The goal is to
interrupt the growth of plasma cells producing the abnormal light-chain antibody proteins. For a number of years,
therapies using melphalan (also known as Alkeran) or cyclophosphamide (Cytoxan) have been the treatment of choice.
Newer drugs that are used in treating multiple myeloma,
such as bortezomib (Velcade), lenalidomide (Revlimid) or
carfilzomib (Kyprolis), also have proved effective. These
therapies are often used in combination with dexamethasone, a steroid to help with the immune response. Undergo27
Chemotherapy followed by stem cell transplantation often
achieves an excellent response, with significant improvement
or stabilization of organ function. However, not all patients
can tolerate this aggressive regimen, particularly those with
advanced heart problems. Given the complexity of the disease, it is recommended that treatment be performed in a
medical center which has experience with amyloidosis (see
the next section). Alternatively, patients can have an initial
evaluation at such a center, with continued communication
during treatment in his or her local community.
Another medicine being developed aims to target directly
the light-chain amyloid deposits which have accumulated
in the body. Currently in clinical trials, this treatment uses
Treatments
28
17. small molecules called monoclonal antibodies to find and
attach specifically to the misfolded proteins of the amyloid
fibrils. The monoclonal antibodies mimic the antibodies that
our immune system naturally produces to protect us from
disease. By targeting and destabilizing the amyloid deposits
in this way, one’s body can potentially identify and remove
them more effectively. In the coming years, this promising
drug may fulfill the final, missing piece of the treatment puzzle in helping to restore organ function and overall health.
AA Amyloidosis
AA (or secondary) amyloidosis is the second most common
form of the disease worldwide. With its associated chronic
inflammatory diseases (e.g., rheumatoid arthritis, Crohn’s
disease, and familial Mediterranean fever), amyloid deposition is very gradual. The survival rate is often more than 10
years, particularly with treatment for kidney disease. In contrast, untreated infections such as osteomyelitis or tuberculosis can cause a quicker accumulation of amyloid.
In all cases, the mainstay of therapy is to address the underlying infection or inflammatory condition. This can slow
or stop the progressive buildup of amyloid by reducing the
circulating precursor protein, serum amyloid A.
Moreover, an oral drug called eprodisate (Kiacta) has been
found to inhibit the formation of amyloid fibrils. Kiacta prevents serum amyloid A from interacting with other molecules
29
that facilitate its misfolding into amyloid. Clinical trials have
shown that, because the amyloid can no longer be formed
and deposited, this treatment can effectively slow or stop
the deterioration of kidney function. It is anticipated that
Kiacta will be approved for widespread use in the next few
years, following the confirmation of its efficacy through international studies.
For those patients with renal failure, dialysis and kidney
transplantation are possible treatments. However, as with
kidney transplants for AL amyloidosis, if the source of the
abnormal protein is not addressed, amyloid may eventually
appear in the donor kidney.
ATTR Amyloidosis
In TTR-mediated familial (or hereditary) amyloidosis, the
heart and nervous system are most commonly affected.
Without intervention, the survival rate ranges between 5-15
years from the onset of the disease.
Since most of the abnormal proteins are produced in the
liver, transplanting the liver can allow for the production of
normal TTR. Waiting periods for organ donation are frequently long, but transplantation is a viable option for some
patients whose disease is not too far advanced.
Meanwhile, new drugs are being developed to prevent
familial amyloid deposits from forming in the first place. As
Treatments
30
18. with liver transplantation, evidence shows that by reducing
the abnormal protein available to become amyloid, organ
function can improve. Two such drugs that may prevent the
mutant TTR from misfolding into amyloid are diflunisal and
tafamidis. These small molecules bind to the precursor proteins and stabilize their structure, so that they do not form
amyloid fibrils and accumulate in the body.
A separate class of drugs using “gene silencing” techniques
heralds a revolution in ATTR treatment. These therapies utilize
the body’s natural process for regulating gene expression.
Very briefly, here is how it works. In our cells, the genes coding for proteins are transcribed from DNA into messenger RNA
(mRNA) molecules. These mRNA are then translated by our
cells’ machinery to produce all of the proteins that make life
possible. With gene-silencing therapy, small RNA-like molecules are carried in the blood to the liver. Once in the cells,
the RNA-based drugs are able to bind specifically with the
mRNA that would produce TTR proteins. When the drugs bind
with the target mRNA, special cellular enzymes (nucleases) will
break down and recycle the mRNA. Therefore, TTR amyloid
production could be slowed or stopped at the source.
Because gene regulation naturally occurs in all human cells,
RNA-based drugs may provide a safe and effective means
to directly prevent the production of abnormal TTR. Administered either intravenously or subcutaneously, initial studies
indicate that there may be a rapid reduction in a patient’s
levels of ATTR protein.
31
It is recommended to visit a medical center with expertise in amyloidosis.
Depending on the type of amyloidosis, treatments may include chemotherapy, cardiac care, organ transplantation or targeted drug therapy.
Treatments
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19. Senile Systemic Amyloidosis
In senile systemic (or age-related) amyloidosis, therapy is
largely supportive for a patient’s cardiac disease. In some
cases, heart transplantation may be done.
For TTR-mediated forms of senile amyloidosis, the same
drug treatments used in familial amyloidosis (e.g., diflunisal,
tafamidis or RNA-based drugs) may inhibit the production
of TTR amyloid. This could help to extend life by preventing
further amyloid formation and deposition in the heart muscle.
Aβ2M Amyloidosis
In Aβ2M (or dialysis-related) amyloidosis, kidney transplantation is considered the best therapeutic option. Low copper dialysis membranes may prevent or delay onset of the disease.
Localized Amyloidosis
For amyloid deposits that occur in isolated areas, such as
the bladder or airways, radiation therapy can slow down the
disease’s progression. Surgical removal of the amyloid deposit may be appropriate once a systemic condition is ruled
out. As with all forms of amyloidosis, patients are encouraged to have periodic checkups to monitor their condition.
For cerebral amyloid angiopathy (CAA) which affects the
brain, there is no known effective treatment. The goal is to
relieve symptoms. This can include medications that help
to improve memory, such as those used to treat Alzheimer’s
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disease. Seizures, sometimes called “amyloid spells,” may
be treated with anticonvulsants such as phenytoin (Dilantin)
or carbamazepine (Tegretol). In some cases, speech and
physical therapies are needed.
Treating the Symptoms of Amyloidosis
It is very important to treat not just the underlying causes of
amyloidosis, but the symptoms of the disease as well. This
will ensure a patient’s quality of life and longevity.
Normal, everyday activities can be carried out as usual.
However, if fatigue or shortness of breath occurs, it is necessary to rest. One should not exert him- or herself beyond
what is recommended by their doctor.
For supportive treatments of the kidneys and heart, patients
may need to take a diuretic drug to pass urine, as prescribed
by their doctors; limit the amount of salt in their diet; or wear
elastic stockings and elevate their legs to lessen the swelling. For the gastrointestinal tract, certain medications can
help with diarrhea and constipation. In general, it may be
useful to make some dietary changes to help relieve symptoms or maintain body weight.
As treatment progresses, damage to the nerves (neuropathy)
can improve. It may take up to 12-24 months for the nerves
to recover, but numbness and weakness can subside. Medications to alleviate pain may be taken orally or applied to the
Treatments
34
20. skin. For discomfort, tingling or burning, the use of a warmwater foot massager for 15 minutes before bed can help with
sleeping. The warm water and vibrations stimulate non-pain
transmitting nerves, and block the pain-transmitting nerves.
Participating in Clinical Research
Clinical trials are research studies that test new ways to diagnose and treat disease. Such research is essential to improve
our understanding of amyloidosis and to develop more effective therapies. The treatments that are available today were all
developed and refined through this ongoing clinical research.
Now patients can achieve durable, long-term remission of
their disease, along with major organ system improvement.
Being involved in clinical research potentially allows patients
to benefit from new, experimental treatments before they are
widely available. In the long run, this leads to improved medicines and therapies for everyone. To learn what clinical trials
are currently recruiting, one may consult with the amyloidosis
centers or visit ‘www.ClinicalTrials.gov’. As well, patients can
search ‘www.PubMed.gov’ to find scientific, peer-reviewed
articles.
For qualifying patients, there is an opportunity to participate
in clinical trials. Whenever new treatments are tested, they
are expected to be as good as or better than the standard
treatments. All proposed clinical trials must be approved and
overseen by an Institutional Review Board (IRB). The IRB is
comprised of physicians, scientists, clergy and lay people.
They are there to ensure the safety of the studies and the accuracy of the results.
The new treatments are evaluated in groups of people who
meet certain requirements for the study. Participation in clinical trials is completely voluntary, and participating patients
sign an informed consent form. It is also okay to withdraw
from the trial at any time. In many cases, the cost of treatment may be covered as part of the study.
35
Early and accurate diagnosis, along with an individualized treatment
plan, are key to achieving positive outcomes for patients and families.
With an extended support community of healthcare providers and peers,
you are not alone.
Treatments
36
21. 6. MAJOR AMYLOIDOSIS CENTERS
There are many qualified physicians to help with diagnosis
and treatment of amyloidosis. As patients, you are not alone.
In the United States, please contact the Amyloidosis Support
Groups for 24-hour help and guidance. The toll-free number is
(866) 404-7539, or email ‘info@amyloidosissupport.com’.
The following is a list of major research and treatment centers
in the United States and internationally. Because amyloidosis
varies with each case, the invaluable expertise of these centers will help to promote positive outcomes for patients and
families.
U.S. Amyloidosis Centers
• Mayo Clinic (Rochester, MN) –
www.mayoclinic.org/amyloidosis
• Boston University Amyloidosis Center (Boston, MA) –
www.bu.edu/amyloid
• Brigham and Women’s Hospital Cardiac Amyloidosis
Program (Boston, MA) –
www.brighamandwomens.org/cvcenter/amyloidosis
• Columbia Multidisciplinary Amyloidosis Program
(New York City, NY) –
www.nyp.org/services/amyloidosis-program-overview.html
• Memorial Sloan-Kettering Cancer Center
(New York City, NY) – www.mskcc.org
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• Mount Sinai Hospital (New York City, NY) –
www.mountsinai.org/patient-care/health-library/diseasesand-conditions/amyloidosis
• Cedars-Sinai Multiple Myeloma & Amyloidosis Program
(Los Angeles, CA) –
www.cedars-sinai.edu/Patients/Programs-and-Services/
Multiple-Myeloma-and-Amyloidosis-Program
• Stanford Amyloid Center (Stanford, CA) –
www.stanfordhospital.org/cardiovascularhealth/amyloid
• Indiana University School of Medicine Amyloid Research
Group (Indianapolis, IN) –
www.iupui.edu/~amyloid/team.htm
International Amyloidosis Centers
• Center for the Study of Familial Amyloidosis
(Rio de Janeiro, Brazil) – www.ceparm.com
• Center for the Study & Cure of Systemic Amyloidosis
(Pavia, Italy) – www.amiloidosi.it
• Groningen Unit for Amyloidosis Research & Development
(The Netherlands) – www.amyloid.nl
• National Centre for Amyloidosis (London, U.K.) –
www.ucl.ac.uk/medicine/amyloidosis
• Princess Alexandra Hospital (Brisbane, Australia) –
www.health.qld.gov.au/pahospital
• Westmead Hospital (Sydney, Australia) –
www.wslhd.health.nsw.gov.au/Westmead-Hospital
• Kumamoto University Hospital (Kumamoto, Japan) –
www.kuh.kumamoto-u.ac.jp
• Princess Margaret Cancer Centre (Toronto, Canada) –
www.theprincessmargaret.ca
Major Amyloidosis Centers
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22. 7. ONLINE RESOURCES
For more information, including local support meetings and
a detailed list of regional doctors, please visit:
Made possible with the support of these
premier diagnostics and therapeutics companies:
Amyloidosis Support Groups
www.AmyloidosisSupport.com
Other helpful resources include:
• Amyloidosis Foundation
www.amyloidosis.org
• Amyloid Support Group U.K.
www.amyloidsupportgroup.co.uk
• Canadian Amyloidosis Support Network
www.thecasn.org
• Leukemia & Lymphoma Society
www.lls.org
• National Organization for Rare Disorders
www.rarediseases.org
• RareConnect
www.rareconnect.org
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www.pfizer.com
www.auventx.com
www.alnylam.com
www.prothena.com
www.millennium.com
www.isisph.com
www.thebindingsite.com
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