This document discusses neurodegenerative diseases, focusing on Alzheimer's disease. It defines neurodegeneration as the progressive loss of neurons, and notes several common neurodegenerative disorders like Parkinson's, Alzheimer's and Huntington's. For Alzheimer's specifically, it describes the disease stages from pre-dementia to advanced, symptoms like memory loss and cognitive decline, pathological features like amyloid plaques and neurofibrillary tangles, potential causes like the amyloid and tau hypotheses, and methods of diagnosis including cognitive testing and brain imaging.
Pharmacotherapy of Alzheimer's disease
Introduction
History
Risk factors
Pathophysiology
Symptoms
Diagnosis
Non pharmacological treatment
Drugs used in treatment of Alzheimer`s
Recent advances
Screening methods
Summary
References
Pharmacotherapy of Alzheimer's disease
Introduction
History
Risk factors
Pathophysiology
Symptoms
Diagnosis
Non pharmacological treatment
Drugs used in treatment of Alzheimer`s
Recent advances
Screening methods
Summary
References
A presentation about Alzheimer's disease, it's definition, it's etiology, its mechanism of development as well as actual treatment and developing treatments.
Molecular Mechanisms of Neurodegeneration: Neurodegenerative Disorders Webin...QIAGEN
Common molecular mechanisms and pathways leading to neurodegeneration, such as Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease or Multiple Sclerosis, are presented in this slideshow. Learn more about research and therapeutic strategies as well as how these discoveries and tools can be used to facilitate your neurodegeneration research.
Definition
Statistics of AD
A brief introduction
Signs and symptoms of AD
NMDA receptors
Classification
Causes
Risk Factors
Pathophysiology
AD… The great unknown
Treatment Options
Future Trends
Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate) and die. Alzheimer's disease is the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently.
Symptoms: Amnesia; Dementia
Diseases or conditions caused: Dementia
Pathophysiology
Pathology
BPharm 2nd Semester
MPharm
Therapeutics
MBBS
Circulating Biomarkers for Alzheimer's Disease: Neurodegenerative Disorders ...QIAGEN
Alzheimer's disease (AD) is a complex neurodegenerative disorder. Circulating miRNAs hold great promise in the discovery of non-invasive and novel biomarkers for AD diagnosis and prognosis. This slideshow presents the role of miRNAs in AD and details current progress in biomarker discovery. Various tools for pathway-focused and genome-wide miRNA expression profiling, miRNA functional studies and target identification are also included.
the feathers of the disease and It is histology
For downloading the presentation, more presentations , infographics and blogs visit :
studyscienceblog.wordpress.com
A presentation about Alzheimer's disease, it's definition, it's etiology, its mechanism of development as well as actual treatment and developing treatments.
Molecular Mechanisms of Neurodegeneration: Neurodegenerative Disorders Webin...QIAGEN
Common molecular mechanisms and pathways leading to neurodegeneration, such as Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease or Multiple Sclerosis, are presented in this slideshow. Learn more about research and therapeutic strategies as well as how these discoveries and tools can be used to facilitate your neurodegeneration research.
Definition
Statistics of AD
A brief introduction
Signs and symptoms of AD
NMDA receptors
Classification
Causes
Risk Factors
Pathophysiology
AD… The great unknown
Treatment Options
Future Trends
Alzheimer's disease is a progressive disorder that causes brain cells to waste away (degenerate) and die. Alzheimer's disease is the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that disrupts a person's ability to function independently.
Symptoms: Amnesia; Dementia
Diseases or conditions caused: Dementia
Pathophysiology
Pathology
BPharm 2nd Semester
MPharm
Therapeutics
MBBS
Circulating Biomarkers for Alzheimer's Disease: Neurodegenerative Disorders ...QIAGEN
Alzheimer's disease (AD) is a complex neurodegenerative disorder. Circulating miRNAs hold great promise in the discovery of non-invasive and novel biomarkers for AD diagnosis and prognosis. This slideshow presents the role of miRNAs in AD and details current progress in biomarker discovery. Various tools for pathway-focused and genome-wide miRNA expression profiling, miRNA functional studies and target identification are also included.
the feathers of the disease and It is histology
For downloading the presentation, more presentations , infographics and blogs visit :
studyscienceblog.wordpress.com
Alzheimer's disease is a causes a progressive loss of brain cells leading to memory loss. In this slide we will learn about its causes,symptoms, pathophysiology, treatment, medication and risk factors.
Alzheimer's disease is a progressive neurologic disorder that causes atrophy of brain cells, leading it to cell death. it is degenerative and progressive illness. Increase in age with sedentary lifestyle and lack of brain storming activities are indirectly leading to mental disorders with cognitive disruptions like dementia and lading up into Alzheimer's, which makes life miserable of client due to dependency. It is essential to keep the elderly active physiologically as well as psychologically. Statistical data of several studies shows the rise in the cases of Alzheimer's disease, which is the highlighting point of concern. Due to increased digitalization and decreased socialization among the human species throughout globe is leading to increased in risk of getting cognitive deficits.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
2. Introduction
Neurodegeneration is the umbrella term for the
progressive loss of structure or function of neurons.
Such as :
Parkinson’s
Alzheimer’s
Huntington’s
There are many parallels between different
neurodegenerative disorders including atypical
protein assemblies as well as induced cell death.
Neurodegeneration can be found in many different
levels of neuronal circuitry ranging from molecular
to systemic.
3. Neurodegenerative disorders
Genetics :Many neurodegenerative diseases
are caused by genetic mutations, most of
which are located in completely unrelated
genes.
In many of the different diseases, the
mutated gene has a common feature: a
repeat of the CAG nucleotide triplet. CAG
encodes for the amino acid glutamine. A
repeat of CAG results in a polyglutamine
(polyQ) tract
4. Proteopathies
That is aggregation of misfolded proteins.
alpha-synuclein: form insoluble fibrils in
pathological conditions ,Lewy bodies, in Parkinson's
disease, dementia with Lewy bodies, and multiple
system atrophy.
In addition, an alpha-synuclein fragment, known as
the non-Abeta component (NAC), is found in
amyloid plaques in Alzheimer's disease.
tau: hyperphosphorylated tau protein is the main
component of neurofibrillary tangles in Alzheimer's
disease.
beta amyloid: the major component of senile
plaques in Alzheimer's disease.
5. Intracellular mechanisms
Protein degradation pathways
Parkinson’s , Huntington’s disease are both
late-onset and associated with the
accumulation of intracellular toxic proteins.
they are primarily caused by aggregates in
the following structures
Cytosol: Parkinson's & Huntington's
Nucleus: Spinocerebellar ataxia type 1 (SCA1)
extracellularly excreted proteins: amyloid-β
in Alzheimer’s disease
6. Eukaryotic correction pathway
Ubiquitin–proteasome: protein ubiquitin along with enzymes is key for
the degradation of many proteins that cause proteinopathies including
polyQ expansions and alpha-synucleins. Decreased proteasome activity
is consistent with models in which intracellular protein aggregates form.
It is still unknown whether or not these aggregates are a cause or a
result of neurodegeneration.
Autophagy–lysosome pathways: a form of programmed cell
death (PCD), this becomes the favorable route when a protein is
aggregate-prone meaning it is a poor proteasome substrate.
This can be split into two forms of autophagy:
1. Macroautophagy is involved with nutrient recycling of macromolecules under
conditions of starvation, certain apoptotic pathways, and if absent, leads to the
formation of ubiquinated inclusions. Experiments in mice with neuronally confined
macroautophagy-gene knockouts develop intraneuronal aggregates leading to
neurodegeneration.
2. Chaperone-mediated autophagy (CMA). defects may also lead to
neurodegeneration. Research has shown that mutant proteins bind to the CMA-
pathway receptors on lysosomal membrane and in doing so block their own
degradation as well as the degradation of other substrates.
7. Mitochondrial dysfunction
The most common form of cell death in neurodegeneration is through
the intrinsic mitochondrial apoptotic pathway.This pathway controls
the activation of caspase-9 by regulating the release of cytochrome
c from the mitochondrial intermembrane space (IMS).
Reactive oxygen species(ROS) are normal byproducts of mitochondrial
respiratory chain activity. ROS concentration is mediated by
mitochondrial antioxidants such as manganese superoxide dismutase
(SOD2) and glutathione peroxidase.
Over production of ROS (oxidative stress) is a central feature of all
neurodegenerative disorders. Mitochondrial disease leading to
neurodegeneration is likely, at least on some level, to involve all of these
functions.
There is strong evidence that mitochondrial dysfunction and oxidative
stress play a causal role in neurodegenerative disease pathogenesis,
including in four of the more well known
diseasesAlzheimer's, Parkinson's, Huntington's, and Amyotrophic
lateral sclerosis.
10. Description
Alzheimer disease, is the most common form
of dementia.There is no cure for the
disease, which worsens as it progresses, and
eventually leads to death.
It was first described by German psychiatrist and
neuropathologist Alois Alzheimer in 1906 and was
named after him.
Most often, AD is diagnosed in people over 65 years
In 2006, there were 26.6 million sufferers worldwide.
Alzheimer's is predicted to affect 1 in 85 people
globally by 2050.
11. Stages
Pre-dementia
Early
Moderate
Advanced
The disease course is divided into four stages, with
progressive patterns
of cognitive and functional impairments.
12. Pre-dementia Stage
The first symptoms are often mistakenly attributed to ageing or stress
These early symptoms can affect the most complex daily living
activities.
The most noticeable deficit is memory loss, which shows up as difficulty
in remembering recently learned facts and inability to acquire new
information.
Subtle problems with the executive
functions of attentiveness, planning, flexibility, and abstract thinking, or
impairments in semantic memory (memory of meanings, and concept
relationships) can also be symptomatic of the early stages of AD.
Apathy can be observed at this stage, and remains the most
persistent neuropsychiatric symptom throughout the course of the
disease
The preclinical stage of the disease has also been termed mild cognitive
impairment
13. Early Stage
In people withAD the increasing impairment of learning and memory eventually
leads to a definitive diagnosis.
In a small portion of them, difficulties with language, executive
functions, perception (agnosia), or execution of movements (apraxia) are more
prominent than memory problems.
AD does not affect all memory capacities equally. Older memories of the
person's life (episodic memory), facts learned (semantic memory), and implicit
memory (the memory of the body on how to do things, such as using a fork to
eat) are affected to a lesser degree than new facts or memories.
Language problems are mainly characterised by a shrinking vocabulary and
decreased word fluency, which lead to a general impoverishment of oral
and written language.
In this stage, the person withAlzheimer's is usually capable of communicating
basic ideas adequately.
While performing fine motor tasks such as writing, drawing or dressing, certain
movement coordination and planning difficulties (apraxia) may be present but
they are commonly unnoticed
14. Moderate Stage
Progressive deterioration eventually hinders independence, with subjects being
unable to perform most common activities of daily living. Speech difficulties
become evident due to an inability to recall vocabulary, which leads to frequent
incorrect word substitutions (paraphasias).
Reading and writing skills are also progressively lost.
Complex motor sequences become less coordinated as time passes and AD
progresses, so the risk of falling increases.
memory problems worsen, and the person may fail to recognise close relatives.
Long-term memory, which was previously intact, becomes impaired.
Behavioural and neuropsychiatric changes: wandering, irritability and labile
affect, leading to crying, outbursts of unpremeditated aggression.
Approximately 30% of people with AD develop illusionary misidentifications and
other delusional symptoms
Subjects also lose insight of their disease process and limitations (anosognosia).
Urinary incontinence can develop.
These symptoms create stress for relatives and caretakers, which can be reduced
by moving the person from home care to other long-term care facilities.
15. Advanced Stage
During the final stage of AD, the person is completely dependent
upon caregivers.
Language is reduced to simple phrases or even single
words, eventually leading to complete loss of speech. Despite
the loss of verbal language abilities, people can often understand
and return emotional signals.Although aggressiveness can still be
present, extreme apathy and exhaustion are much more
common results. ]
Muscle mass and mobility deteriorate to the point where they are
bedridden
lose the ability to feed themselves.
AD is a terminal illness, with the cause of death typically being an
external factor, such as infection of pressure
ulcers or pneumonia, not the disease itself.
16. Causes
The cause for most Alzheimer's cases is still
essentially unknown (except cases where
genetic differences have been identified).
Several competing hypotheses exist trying to
explain the cause of the disease:
1. Cholinergic hypothesis
2. Amyloid hypothesis
3. Tau hypothesis
4. Other hypotheses
17. Cholinergic hypothesis
The oldest, on which most currently available drug
therapies are based, is the cholinergic hypothesis.
which proposes that AD is caused by reduced
synthesis of the neurotransmitter acetylcholine.
The cholinergic hypothesis has not maintained
widespread support, largely because medications
intended to treat acetylcholine deficiency have not
been very effective.
Other cholinergic effects have also been
proposed, for example, initiation of large-scale
aggregation of amyloid,leading to generalised
neuroinflammation.
18. Amyloid hypothesis
the amyloid hypothesis postulated that beta-amyloid (βA) deposits are
the fundamental cause of the disease.[
Support for this postulate comes from the location of the gene for
the amyloid precursor protein (APP) on chromosome 21, together with
the fact that people with trisomy 21 (Down Syndrome) who have an
extra gene copy almost universally exhibitAD by 40 years of age.
Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk
factor for AD.Whilst apolipoproteins enhance the break down of beta
amyloid, some isoforms are not very effective at this task (such as
APOE4), leading to excess amyloid buildup in the brain
In 2009, this theory was updated, suggesting that a close relative of the
beta-amyloid protein, and not necessarily the beta-amyloid itself, may
be a major culprit in the disease.
The theory holds that an amyloid-related mechanism that prunes
neuronal connections in the brain in the fast-growth phase of early life
may be triggered by ageing-related processes in later life to cause the
neuronal withering ofAlzheimer's disease.
19. Histopathologic image of senile plaques seen in
the cerebral cortex of a person with Alzheimer's
disease of presenile onset.
Enzymes act on the APP (amyloid precursor protein) and cut it into fragments.
The beta-amyloid fragment is crucial in the formation of senile plaques in AD.
Senile plaques
20. Tau hypothesis
The tau hypothesis is the idea that tau
protein abnormalities initiate the disease
cascade.
In this model, hyperphosphorylated tau begins
to pair with other threads of tau. Eventually, they
form neurofibrillary tangles inside nerve cell
bodies.
When this occurs, the microtubules
disintegrate, collapsing the neuron's transport
system.
This may result first in malfunctions in
biochemical communication between neurons
and later in the death of the cells.
21. Tau protein
Tau proteins are proteins that stabilize microtubules.They
are abundant in neurons of the central nervous system and
are less common elsewhere, but are also expressed at very
low levels in CNS astrocytes and oligodendrocytes.
When tau proteins are defective, and no longer stabilize
microtubules properly, they can result in dementias such
asAlzheimer's disease.
In other neurodegenerative diseases, the deposition of
aggregates enriched in certain tau isoforms has been
reported.When misfolded, this otherwise very soluble
protein can form extremely insoluble aggregates that
contribute to a number of neurodegenerative diseases.
22. Changes in tau protein
InAlzheimer's
disease, changes
in tau protein
lead to the
disintegration of
microtubules in
brain cells.
23. Other hypotheses
Herpes simplex virus type 1 has also been proposed to play a
causative role in people carrying the susceptible versions of
the apoE gene.
age-related myelin breakdown in the brain. Iron released during
myelin breakdown is hypothesised to cause further damage.
Homeostatic myelin repair processes contribute to the
development of proteinaceous deposits such as beta-amyloid
and tau.
Oxidative stress and dys-homeostasis of biometal
(biology) metabolism may be significant in the formation of the
pathology.
AD individuals show 70% loss of locus coeruleus cells that
provide norepinephrine.
This suggests that degeneration of the locus ceruleus might be
responsible for increased βA deposition in AD brains.
24. Pathophysiology
Neuropathology
Alzheimer's disease is characterised by loss of neurons and synapses in
the cerebral cortex and certain subcortical regions.This loss results in
gross atrophy of the affected regions, including degeneration in the temporal
lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.
Studies using MRI and PET have documented reductions in the size of specific
brain regions in people with AD as they progressed from mild cognitive
impairment to Alzheimer's disease, and in comparison with similar images from
healthy older adults.
Both amyloid plaques and neurofibrillary tangles are clearly visible
by microscopy in brains of those afflicted byAD. Plaques are dense,
mostly insoluble deposits of beta-amyloid peptide and cellular material outside
and around neurons.Tangles (neurofibrillary tangles) are aggregates of the
microtubule-associated protein tau which has become hyperphosphorylated and
accumulate inside the cells themselves.Although many older individuals develop
some plaques and tangles as a consequence of ageing, the brains of people with
AD have a greater number of them in specific brain regions such as the temporal
lobe. Lewy bodies are not rare in the brains of people withAD.
25. Biochemistry
Alzheimer's disease has been identified as a protein
misfolding disease (proteopathy), caused by accumulation of
abnormally folded amyloid beta and amyloid tau proteins in the
brain
Plaques are made up of small peptides, 39–43 amino acids in
length, called beta-amyloid (Aβ).
Beta-amyloid is a fragment from a larger protein called amyloid
precursor protein (APP), a transmembrane protein that
penetrates through the neuron's membrane. APP is critical to
neuron growth, survival and post-injury repair.
In Alzheimer's disease, an unknown process causes APP to be
divided into smaller fragments by enzymes through proteolysis
One of these fragments gives rise to fibrils of beta-
amyloid, which form clumps that deposit outside neurons in
dense formations known as senile plaques
26. Diagnosis
Alzheimer's disease is usually diagnosed clinically from the
patient history, collateral history from relatives, and clinical
observations, based on the presence of
characteristic neurological and neuropsychological features and
the absence of alternative conditions.
Advanced medical imaging with computed tomography (CT)
or magnetic resonance imaging (MRI), and with single photon
emission computed tomography (SPECT) or positron emission
tomography (PET) can be used to help exclude other cerebral
pathology or subtypes of dementia.
Moreover, it may predict conversion from prodromal stages
(mild cognitive impairment) to Alzheimer's disease.
Assessment of intellectual functioning including memory testing
can further characterise the state of the disease.
Medical organisations have created diagnostic criteria to ease
and standardise the diagnostic process for practicing physicians.
27. NINCDS-ADRDA Alzheimer's
Criteria
The National Institute of Neurological and Communicative
Disorders and Stroke (NINCDS) and the Alzheimer's Disease and
Related Disorders Association (ADRDA, now known as
theAlzheimer's Association) established the most commonly
used NINCDS-ADRDA Alzheimer's
These criteria require that the presence of cognitive
impairment, and a suspected dementia syndrome, be confirmed
by neuropsychological testing for a clinical diagnosis of possible
or probable AD.
A histopathologic confirmation including
a microscopic examination of brain tissue is required for a
definitive diagnosis
Eight cognitive domains are most commonly impaired in AD—
memory, language, perceptual skills, attention, constructive
abilities, orientation, problem solving and functional abilities.
28. PET scan of the brain of a person with AD showing a
loss of function in the temporal lobe
Neuropsychological screening tests can help in the
diagnosis of AD. In the tests, people are instructed
to copy drawings similar to the one shown in the
picture, remember words, read, and subtract serial
numbers.
29. Pet scan showing Alzheimer disease
beta amyloid deposits and a normal
control one.
30. Prevention
cardiovascular risk factors, such
as hypercholesterolaemia, hypertension, diabetes, and smoking, are
associated with a higher risk of onset and course of.
The components of a Mediterranean diet, which include fruit and
vegetables, bread, wheat and other cereals, olive oil, fish, and red
wine, may all individually or together reduce the risk a
Long-term usage of non-steroidal anti-inflammatory drug (NSAIDs) is
associated with a reduced likelihood of developing AD .
NSAIDs can reduce inflammation related to amyloid plaques
A 21-year study found that coffee drinkers of 3–5 cups per day at
midlife had a 65% reduction in risk of dementia in late-life.and course of
Alzheimer's disease.
People who engage in intellectual activities such as reading, playing
board games, completing crossword puzzles, playing musical
instruments, or regular social interaction show a reduced risk for
Alzheimer's disease
31. Two studies have shown that medical
cannabis may be effective in inhibiting the
progress of AD.The active ingredient in
marijuana,THC, may prevent the formation of
deposits in the brain associated with Alzheimer's
disease.THC was found to inhibit
acetylcholinesterase more effectively than
commercially marketed drugs
f
32. Management
Five medications are currently used to treat the cognitive
manifestations ofAD: four are acetylcholinesterase
inhibitors (tacrine, rivastigmine, galantamine and donepezil
) and the other (memantine) is an NMDA receptor
antagonist
No drug has an indication for delaying or halting the
progression of the disease.
Memantine (brand names Akatinol) is a
noncompetitive NMDA receptor antagonist first used as an
anti-influenza agent. It acts on the glutamatergic system by
blocking NMDA receptors and inhibiting their
overstimulation by glutamate.
33. Prognosis
The early stages of Alzheimer's disease are difficult to diagnose. A definitive
diagnosis is usually made once cognitive impairment compromises daily living
activities, although the person may still be living independently.
The symptoms will progress from mild cognitive problems, such as memory loss
through increasing stages of cognitive and non-cognitive
disturbances, eliminating any possibility of independent living, especially in the
late stages of the disease.
Life expectancy of the population with the disease is reduced
The mean life expectancy following diagnosis is approximately seven years
Fewer than 3% of people live more than fourteen years
Other coincident diseases such as heart problems, diabetes or history of alcohol
abuse are also related with shortened survival
Men have a less favourable survival prognosis than women.
The disease is the underlying cause of death in 70% of all cases
Pneumonia and dehydration are the most frequent immediate causes of
death, while cancer is a less frequent cause of death than in the general
population.
34. Research directions
Reduction of beta-amyloid levels is a common target of compounds
apomorphine under investigation.
Immunotherapy or vaccination for the amyloid protein is one treatment
modality under study
It is based upon the concept of training the immune system to recognise, attack,
and reverse deposition of amyloid, thereby altering the course of the disease
bapineuzumab, an antibody designed as identical to the naturally induced anti-
amyloid antibody
methylthioninium chloride (trade name rember), a drug that inhibits tau
aggregation,
The common herpes simplex virus HSV-1 has been found to colocate with
amyloid plaques.[This suggested the possibility thatAD could be treated or
prevented with antiviral medication.[
An FDA panel voted unanimously to recommend approval of florbetapir, which is
currently used in an investigational study.The imaging agent can help to detect
Alzheimer's brain plaques, but will require additional clinical research before it
can be made available commercially.
35. Famous persons with AD
Ronald Reagan (1911-2004): Six years after the end
of his presidency,Ronald Reagan announced to the
American public that he was “one of the millions of
Americans who will be afflicted with Alzheimer’s
disease.” He said that his public disclosure was
intended to raise public awareness about the disease.
Sugar Ray Robinson (1921-1989): Sugar Ray
Robinson, recognized as one of the best boxers
ever, died from Alzheimer’s disease at just 67 years of
age. Robinson held the welterweight and
middleweight title belts, and finished with a final
record of 173 wins, 19 losses, and 2 draws. It’s not
currently known whether head injuries can contribute
toAlzheimer’s disease.
Charles Bronson (1921 – 2003): Charles Bronson, star
of DeathWish and numerous other action films, spent
the last years of his life debilitated from Alzheimer’s.
Auguste Deter he is not a celebrity- but the first
person diagnosed with Alzheimer’s disease .Alois
Alzheimer's patient in 1902.
36. James Doohan :A Canadian
character and voice
actor, best known for his role
in the StarTrek series.
Sir Charles Kuen
Kao: British electrical
engineer and physicist who
pioneered in the
development and use of fiber
optics in
telecommunications