KURSK STATE MEDICAL UNIVERSITY
FACULTY OF FOREIGN MEDICINE
Department of Pathological Anatomy
Course research work of pathological anatomy
Theme: Degenerative brain disorder in aging people
Student: Gustavo Duarte Viana
3rd year 2nd semester
Supervisor: associated professor Goryainova, G. A.
• General Considerations
• Basic concept of dementia
• Most common degenerative disease list
• Alzhimer’s disease
• Pick’s disease
• Parkinson’s disease
• Huntington’s disease
• Amyotrophic lateral sclerosis
Degenerative disorders occurs during aging and may worse with time, in contrast the youth
brain disorders is infectious more than degenerative one.
DEGENERATIVE DISEASES are Gray matter disease with progressive loss of neurons and
secondary changes in white matter tracts.
Degenerative manifests as disturbed organism with inclusions according the inside of the cells
contents and atrophy of the cells and loss of cells.
it mainly occur in patients without clear inciting event of previous neurologic deficits, it has
Intracellular abnormalities and only loss of affected neurons
DEGENERATIVE DISEASES are Grouped according to anatomic regions affected:
CEREBRAL CORTEX – Alzheimer disease, Pick’s disease
SUBCORTICAL AREAS – movement disorders (tremors and dyskinesia): Parkinsonism,
Huntington’s chorea, etc.
Motor neurons of spinal cord: Amyotrophic lateral sclerosis
• The etiology is classified as primary or secondary according to neurological
or systemic causes
Global – Alzheimer & Lewibody
Selective/System – Parkinsons , Huntingtons , MND.
Secondary Degenerations: Toxic, metabolic(storage), infections,
nutritional. Alcohol & B12 deficiency, Cerebrovascular disease – stroke.
Infections (e.g. Creutzfeldt-Jakob, syphilis, HIV.), neoplasma, heamatoma,
hydrocephalus and etc.
Basic concept of Dementia
Dementia: Acquired global impairment of intellect-intact consciousness >
15% of adults over 80 are demented. Primary & secondary degenerative
disorders cause dementias.
Dementia (taken from Latin, originally meaning "madness", from de"without" + ment, the root of mens "mind“) is a chronic or persistent
disorder of the mental processes caused by brain disease or injury and
marked by memory disorders, personality changes, and impaired
reasoning more than expected in normal aging.
Most common degenerative disease list
• There are many degenerative diseases recognized, we are going to
speculate the five most common types:
Amyotrophic lateral sclerosis (ALS)
• ALZHEIMER DISEASE DEMENTIA is acquired or inherited disorder of
progressive loss of cognitive function independent of the state of
• Insidious impairment of higher intellectual function, mood and behavioral
• progressive disorientation, memory loss, aphasia
• 5 to 10 yrs – disabled, mute, immobile
• Mostly sporadic, elderly – major medical, social and economic problems
History of Alzheimer’s disease
It was first described by German psychiatrist and neuropathologist Alois
Alzheimer in 1906 and was named after him. Alois Alzheimer was a
talented Doctor which with the difficulties at that time he developed and
used new technologies and new staining to investigate the slices of
normal and demented patients and he observed many characteristics
which is even today the defining key of Alzheimer
Statistic for Alzheimer’s disease rate according
By this graphic we may conclude that aging and women are really a risk factor
for Alzheimer’s development.
• Alzheimer’s disease rate according to race In this graphic we see that
Hispanic and Africans are essentially predisposed to Alzheimer disease.
(Theory of gene for APOE4 )
Risk factors for Alzheimer
• Aging: (in contrast to what Alois Alzheimer said, the AD is more
susceptible in aging)
• Family History: Genetic play a important role, Apolipoprotein E is a normal
protein produced in the body, by the genetic difference there are 3 types
E2, E3 and E4, E4 is highly related to alzheimer, 60% are carrier of APO E4.
• Down syndrome people are more susceptible to Alzheimer and it is in
• Head Injury
• Low education
• Mental inactivity
• Sedentary lifestyle
• Cerebrovascular disease
• Diet in low fat
Three metals which can be the cause of Alzheimer
The scientists now are thiking about the theory that 3 main metals
are strongly linked with Alzheimer’s disease, it is already know that
they are neurotoxic and we should keep the balance required daily of
It's the fuel that allows red blood cells to transport oxygen
throughout the body. But when it comes to brain health, a 2011
study in the journal Neurology showed that people with high
hemoglobin (an indicator of iron levels) were more than three times
as likely to develop Alzheimer's as those with levels in a healthy
Get smart: Go easy on meat -- it's loaded with easily absorbable
heme iron, which your body can't regulate well. Dark leafy greens
can help you meet the recommended daily allowance (RDA) for iron
(18 mg for women ages 19 to 50; 8 mg for women 50+). They're also
rich in antioxidants that "bind to iron so it can't cause as much
damage," says UCLA psychiatry professor George Bartzokis, MD.
Quick fix: Swap out your cast-iron pans for stainless steel. One study
found that the iron content of spaghetti sauce increased more than
nine times after being cooked in a cast-iron skillet.
The aluminum-Alzheimer's link remains hotly contested, but most
experts agree that the metal can be a neurotoxin. Although our
bodies don't need aluminum to function, it seeps in through antacids
("they can deliver a hundred times more aluminum than you'd get
from a day's worth of food," Barnard says); soda cans, which can
leach aluminum; and tap water (aluminum can be introduced during
purification). In one British study, people with high levels of
aluminum in their tap water had a 50 percent increased risk for
Alzheimer's compared to those with the least exposure.
Get smart: Call your local water supplier and ask for the aluminum
level. "If your city's range is anything higher than undetectable,
install an under-sink filter," Barnard says.
Quick fix: Store your leftovers in glass; acidic foods like pizza or
pasta sauce can absorb aluminum from foil.
Dietary copper (in foods like shellfish, nuts, and beans) is generally
safe. But inorganic copper -- the type in multivitamins and tap water
-- largely bypasses the liver's filtration system and heads directly to
the blood and brain. It's especially dangerous when combined with
saturated and trans fats: Research has found that individuals whose
high-fat diets included 1.6 or more mg of copper a day experienced a
loss of mental function equivalent to an extra 19 years of aging,
compared with those who took in an average of 0.9 mg a day.
Get smart: Check your pipes. If you have copper plumbing, let the
water run for a minute in the morning before drinking from the tap,
to flush out any copper that may have built up overnight.
Macromorphology: Cortical atrophy: wide sulci (frontal, temporal, parietal lobes),
Cortical atrophy: wide sulci (frontal, temporal, parietal lobes), narrowed gyri,
compensatory ventricular enlargement (hydrocephalus ex vacuo)
Microscopic Morphology of Alzheimer’s disease
• Neuritic (senile) plaques: dystrophic neurites, amyloid core of Aβ from
APP (amyloid precursor protein), it forms grey-pink formations in the
cortex and more rare in the subcortical region, their sizes are about
20mm-2cm in diameter and hard, it is stained by congo red because of
• Neurofibrillary tangles: disorder of the normal skeleton of the neurons in
Alzheimer's neurofibers, it contain hyperphosphorylated form of protein
tau, it forms big bands instead of thin, this protein is need in norm to
make the roles for passage of nutrients to the cells.
• Amyloid angiopathy: narrowed lumens with thikened walls and it depends
according of the amyloid concentration.
1. Earliest in the entorhinal cortex
2. Spread to hippocampal formation and isocortex
3. Extend to the neocortex
Senile plaques accumulation of beta amyloid and Tangles which are
Nuerofibrillary tau protein.
Microscopically showing Plaques and tangles
Amyloid angiopathy by congo red
• Progression is slow (> 10 yrs) but relentless
• Initial symptoms – forgetfulness
• Language deficits, loss of mathematical skills, loss of learned motor skills
• Final stage: incontinent, mute, unable to walk with intercurrent disease,
Picks is a disease of the brain, it is a rare form of dementia and is very serious
and my be fatal.
It makes a lot of damage to the brain specially in the frontal and parietal lobes, it
is a slow process and takes a while to damage the brain enough that the patient
cant remember basically anything.
People with pick’s disease have pick bodies inside their brain, pick’s bodies have
certain type off cell in them that needs a great amount of protein (tau), the brain
cells shrink and patient lose the memory. Doctors haven't yet discovered clearly
what cause the pick’s diesase, there is a theory that is genetically transferred.
The patient with Pick’s disease and details:
Age in between 45-65.
repeated speech because don’t remember if they said or not
limited and problems during speech
sometimes they are unable to talk at all, because lost all speech area in
the frontal lobe, thus they describe what they want instead.
• The patient usually die due to infections such as pneumonia.
Micro: Hippocampus stained with anti-tau antibody. Many neuronal cell bodies
contain sharply circumscribed, spherical cytoplasmic inclusion bodies (Pick
• Establish diagnosis: there are a lot of parkinsonism and not all are
• Age: there are differently treated and thus age has a lot to imply.
• Disability (symptoms and severity) e.g Artist and pensionist.
• Tremor (rest)
• Decrease facial expression (Mask or parkinsonian face)
• Stooped posture
• Micrographia/ hypophonia
Some feature of a parkinsonian patients below
Test of cogweel and patient with rolling pill hand movement
Not all Parkinsonians are Parkinson’s disease:
• Neurodegenerative disorders
• Secondaty parkinsonims
Multiple system atrophy (MSA)
Diffuse lewi bodies disease
Normal pressure hydrocephalus
Specific features of Parkinson's disease to distinguish between others
Pyramidal tract signs
Causes for Parkinson’s disease
• Idiopathic (free radical-induced
• Immunological theory
(antibodies against the
• Drug-induced (heroin)
• Toxic damage (CO, manganese
Statistics on Parkinson’s disease
Parkinson rate according to age
We conclude that the Parkinson increase with aging process and the pick
is about 60-64 years old
Parkinson rate according to countries
By this map we can conclude that the incidence for Parkinson is higher in
most of the cases in high developed countries which people live a longer
No specific, standard criteria exist for the neuropathologic diagnosis of Parkinson
disease, as the specificity and sensitivity of its characteristic findings have not
been clearly established. However, the following are the 2 major neuropathologic
findings in Parkinson disease:
• Loss of pigmented dopaminergic neurons of the substantia nigra pars
The loss of dopamine neurons occurs most prominently in the ventral lateral
substantia nigra. Approximately 60-80% of dopaminergic neurons are lost before
the motor signs of Parkinson disease emerge.
• The presence of Lewy bodies and Lewy neurites
Some individuals who were thought to be normal neurologically at the time of
their deaths are found to have Lewy bodies on autopsy examination. These
incidental Lewy bodies have been hypothesized to represent the presymptomatic
phase of Parkinson disease. The prevalence of incidental Lewy bodies increases
with age. Note that Lewy bodies are not specific to Parkinson disease, as they are
found in some cases of atypical parkinsonism, Hallervorden-Spatz disease, and
other disorders. Nonetheless, they are a characteristic pathology finding of
• Pathology Pallor of the substantia nigra; decrease in number of pigmented
neurons and other neurons in the same region show shrinkage and
• Loss of neurons replaced by macrophage
• Marked degree of astrocyte gliosis.
• Lewy bodies (hyaline bodies)
Macro Specimen in Parkinson’s disease
Macro specimen in cross section of the mesencephalon showing the
disappearance of substantia nigra containing dopaminergic neurons.
Macro specimen showing the disappearance of substantia nigra and in micro the
the intracytoplasmic lewy body.
Prognosis of Parkinson’s disease
The severity of Parkinson's disease symptoms vary greatly from individual to
individual and it is not possible to predict how quickly the disorder will progress.
Parkinson's disease itself is not a fatal disease, and the average life expectancy is
similar to that of people without the disease. Secondary complications, such as
pneumonia, falling-related injuries, and choking can lead to death. There are
many treatment options that can reduce some of the symptoms and can prolong
the quality of life of an individual with Parkinson's diseas
• HD runs in family and affects about 110,000 people in western countries,
and those people have 50% chance to pass it on each time they have a
• It cause the brain to malfunction, which cause the people with HD to have
problems in movement, thinking and mood.
• The symptoms starts aroud 30-50 for most of HD patients, but 6% may
develop it in childhood and most patients die after 20-30 years after the
In the DNA there is a sequence of CAG in the DNA structure, this is a abnormal
sequence and it starts to produce a 36 aminopeptide of glutamete which is toxic
to the glutaminergic neurons in the basal ganglia, specially the striatal.
This protein accumulates in the neurons and interfere with the functional system
of the cells and leading to its death.
• It is a neurodegenerative disorder specifically in the basal ganglia.
• Basal ganglia helps us to control the movement that we want to start or
stop and organize thoughts and regulate emotion, thus the disease cause
the neurons in the basal ganglia to degenerate and thus arising the
Small brain, atrophy of caudate nucleus and putamen, Secondarily
atrophic globus, pallidus and dilated ventricles, Frontal and less often
parietal, severe loss of striatal neurons with fibrillary gliosis
The difference between a normal brain and a HD brain
Symptoms of Huntington’s disease
1) Movements are the most significant, they feels restlessness and jerking
2) Loss of control of emotion: said, anxiety, aggressive and social
4) it begins to be difficult to talk, walk, writting and solving tasks
5) Loss of attention and cant organize the thoughts
6) Difficult to thinking.
• There is no cure for the disease, there are only palliative treatment to
relieve the symptoms like Chorea, instability of emotions, depression and
• The lifetime of the disease is around the age of 40 or 50.
Amyotrophic sclerosis, Motor neurone disease or Lou
Degenerative disorder of the peripheral nervous system
• Degeneration and death of motor nerves
– Upper Motor Neuron
• within brain/spinal cord
– Lower Motor Neurons
• leaves brain (stem)/spinal cord
• Relatively spared
– Eye movements and bowel/bladder function
• Etiology – unknown
• Average age of onset mid-50’s
• Mode of transmission
– Sporadic – 90-95%
– Familial – 5-10% (autosomal dominant)
• Male : Female – 3:2
• Lower motor neuron signs
– Weakness, muscle wasting, hyporeflexia, muscle cramps, fasciculations
• Upper motor neuron signs
– Spasticity, hyperreflexia, weakness, faciculations
• Asymmetric Weakness – most common
• Onset single limb or bulbar
• Local spread then regional spread
– Bulbar, cervical, thoracic, lumbosacral
The dying neurons are replaced with proliferating astrocytes (a type of glial cell) in
a process known as gliosis. This proliferation of glial cells leads to "glial scarring".
In addition, amyotrophic lateral sclerosis neurons also have intracellular
inclusions when viewed under the microscope. These inclusions are composed of
different abnormal protein molecules that can be phosphorylated or ubiquinated.
A specific type of inclusion known as a Bunina body is also commonly seen.
Prognosis for amyotrophic lateral sclerosis
• ALS is a fatal disease. Median survival is 3 years from clinical onset of
weakness. However, longer survival is not rare. About 15% of patients with
ALS live 5 years after diagnosis, and about 5% survive for more than 10
years. Long-term survival is associated with a younger age at onset, being
male, and limb (rather than bulbar) symptom onset. Rare reports of
spontaneous remission exist
In general overview degenerative disease are more prevalent in aging people
than in young people, in young people it’s more prevalent infectious disease, it
affects people nearby to the age of 60 years old and it is a disease more
distributed in well developed countries because of the long life time of the
citizens, but it not only aging is a major factor for degenerative disorders, the
sex is a factor also which differ from each disease, for example men are more
predisposed to Parkinson and women are predisposed to Alzheimer’s disease.
Also genetic plays a very important role in all degenerative disease, like in
Alzheimer by finding the high level of APOE4 (Apo lipoprotein E4) in people
from Nepal and other countries which the life time is shorter than in well
developed countries, there are many factors like low educations (may be
people which are high educated have a high financial status), stress,
professional occupation, sleep disorders, head injury which caused changes in
brain architecture, estrogen replacement therapy, pharmacological therapy
(often may lead to parkinsonism), and so on, these factors can lead to
degenerative disorders or can progress them to a grave stage.
Unfortunately science didn’t find the radical cure for these diseases, but they
are trying and there are many palliative pharmacological therapies to
minimize their suffering and give them a better life, we should always have
patience with such patients, because they are aware that they are not as they
were before as person and because of this may lead to a very profound
depression and may worse the stage of the disease, we should motivate them
to go on and make them hope for a better time to come.
Harrison’s principles of Internal Medicine, 16th edition, chapter 350, pag 2393,
Alzheimer’s Disease and other Dementias, by thomas D. bird/ Bruce L. Miller.
Harrison’s principles of Internal Medicine, 16th edition, chapter 351, Pag 2406,
Parkinson’s Disease and other Movement disorders, by Mahlon R. Delong/ Jorge
Harrison’s principles of Internal Medicine, 16th edition, chapter 353, Pag 2424,
Amyotrophic lateral Sclerosis and others motor neuron disease,