Principles and practice of Human Pathology – Lecture 10 + 11 (25-5-2018):
Pathology of the Nervous System (Alzheimer’s disease)
Alzheimer’s disease = dementia, dementia is not alzheimer’s disease, because
dementia is a common name for a number of syndromes that lead to cognitive
declines. Alzheimer’s disease is the most prevalent one.
There are also:
- Vascular dementia
- Frontotemporal dementia
Risk factors for Alzheimer’s disease:
- Age (the older you get, the more chance on Alzheimer, especially between 60-
89)
o Below the age of 65 early onset Alzheimer’s disease
o Above the age of 65 late onset Alzheimer’s disease
More women are affected than men.
Alzheimer’s disease:
- Most prevalent form of dementia (50%)
- Sporadic progressive neurodegenerative disorder (no genetic/familial
inheritance involved, it occurs randomly)
o progressive: severity of the disease increases overtime
o Neurodegenerative: neuronal cell loss in the brain
Dr. Alois Alzheimer was the first person to describe a link between the clinical
symptoms of a patient with dementia and the neuropathological findings.
Characteristics of Alzheimer’s:
- Memory disturbances
- Language problems
- Problems with praxis
- Problems with visual recognition
- Disturbances in executive functions
- Disorientation
- Psychosis
- Depression, hallucinations
Patients remember things from long times ago, rather than things that just happened.
Neuropathology Alzheimer:
Atrophy of the brain (tissue is lost) there is less tissue in the brain (resulting in
more space).
±1,5kg is the average weight of a normal brain, in Alzheimer’s disease in the most
extreme cases a brain weighs around ±1kg.
Differences Alzheimer’s vs normal brain:
- Bigger ventricles (hersenkamers)
, o These ventricles normally contain CSF (cerebral spinal fluid), but due to
atrophy these ventricles are enlargened.
- Gray matter is lost/has diminished.
o Gray matter is the outside of the brain, contains cell bodies.
White matter: extensions of neurons.
The hippocampus is degenerated to almost nothing, in the Alzheimer’s disease brain.
The hippocampus has an important function in memory, therefore this degeneration
links to memory disorders.
Microscopic lesions:
Characteristic lesions in Alzheimer’s patients brain:
1. Neurofibrillary tangles:
Intracellular lesions, intracellular aggregation of proteins.
Everything that is black is abnormal, due to the silver staining color shows
aggregated (abnormal) protein
Tau protein accumulates.
2. Senile plaques:
Extracellular lesions, extracellular aggregation of proteins.
Amyloid B protein accumulates:
- In between the neuronal cells
- In the walls of the brain vasculature
All brown staining (immunohistochemistry) is Amyeloid B protein.
Alzheimer’s disease metabolism:
Abnormally folded proteins:
1. Tau protein:
Electron microscope is used to show these tangles; composed of paired helical
filaments (bundles which twist around each other).
Tau protein binds to microtubules in the neuron (which are the cytoskeleton of the
neuron). Tau protein becomes hyperphosphorylated (extra phosphor is added)
leads to detachment of Tau protein from the microtubules.
- Consequence 1: microtubules disintergrate, because they need Tau to
function well
- Consequence 2: release of hyperphosphorylated Tau protein, which then
aggregates to itself.
These consequences lead to neuronal death.
Hyperphosphorylation happens by kinases
Dephosphorylation normally occurs through phosphatases
In Alzheimer’s disease: decreased activity of phosphatases therefore higher
amount of phosphorylation.
Pathology of the Nervous System (Alzheimer’s disease)
Alzheimer’s disease = dementia, dementia is not alzheimer’s disease, because
dementia is a common name for a number of syndromes that lead to cognitive
declines. Alzheimer’s disease is the most prevalent one.
There are also:
- Vascular dementia
- Frontotemporal dementia
Risk factors for Alzheimer’s disease:
- Age (the older you get, the more chance on Alzheimer, especially between 60-
89)
o Below the age of 65 early onset Alzheimer’s disease
o Above the age of 65 late onset Alzheimer’s disease
More women are affected than men.
Alzheimer’s disease:
- Most prevalent form of dementia (50%)
- Sporadic progressive neurodegenerative disorder (no genetic/familial
inheritance involved, it occurs randomly)
o progressive: severity of the disease increases overtime
o Neurodegenerative: neuronal cell loss in the brain
Dr. Alois Alzheimer was the first person to describe a link between the clinical
symptoms of a patient with dementia and the neuropathological findings.
Characteristics of Alzheimer’s:
- Memory disturbances
- Language problems
- Problems with praxis
- Problems with visual recognition
- Disturbances in executive functions
- Disorientation
- Psychosis
- Depression, hallucinations
Patients remember things from long times ago, rather than things that just happened.
Neuropathology Alzheimer:
Atrophy of the brain (tissue is lost) there is less tissue in the brain (resulting in
more space).
±1,5kg is the average weight of a normal brain, in Alzheimer’s disease in the most
extreme cases a brain weighs around ±1kg.
Differences Alzheimer’s vs normal brain:
- Bigger ventricles (hersenkamers)
, o These ventricles normally contain CSF (cerebral spinal fluid), but due to
atrophy these ventricles are enlargened.
- Gray matter is lost/has diminished.
o Gray matter is the outside of the brain, contains cell bodies.
White matter: extensions of neurons.
The hippocampus is degenerated to almost nothing, in the Alzheimer’s disease brain.
The hippocampus has an important function in memory, therefore this degeneration
links to memory disorders.
Microscopic lesions:
Characteristic lesions in Alzheimer’s patients brain:
1. Neurofibrillary tangles:
Intracellular lesions, intracellular aggregation of proteins.
Everything that is black is abnormal, due to the silver staining color shows
aggregated (abnormal) protein
Tau protein accumulates.
2. Senile plaques:
Extracellular lesions, extracellular aggregation of proteins.
Amyloid B protein accumulates:
- In between the neuronal cells
- In the walls of the brain vasculature
All brown staining (immunohistochemistry) is Amyeloid B protein.
Alzheimer’s disease metabolism:
Abnormally folded proteins:
1. Tau protein:
Electron microscope is used to show these tangles; composed of paired helical
filaments (bundles which twist around each other).
Tau protein binds to microtubules in the neuron (which are the cytoskeleton of the
neuron). Tau protein becomes hyperphosphorylated (extra phosphor is added)
leads to detachment of Tau protein from the microtubules.
- Consequence 1: microtubules disintergrate, because they need Tau to
function well
- Consequence 2: release of hyperphosphorylated Tau protein, which then
aggregates to itself.
These consequences lead to neuronal death.
Hyperphosphorylation happens by kinases
Dephosphorylation normally occurs through phosphatases
In Alzheimer’s disease: decreased activity of phosphatases therefore higher
amount of phosphorylation.
