Pathology 3500 Lecture Notes - Lecture 38: Substantia Nigra, Gear, Presenilin
1 May 2018
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Alzheimer's Pathology
● Gross
○ Space between the gyri is enlarged
● Tangles
○ Deposit of abnormal proteins within the terminal process of neurons
○ Makes it difficult for axons to connect
Alzheimer’s Pathogenesis
● 80% are sporadic (no identified risk factor)
● 20% are hereditary
● APP gene mutations
● Presenilin gene mutations, etc
● Apo E genotype
○ 3 different allelic forms (E2, E3, E4)
■ Different version have different ability to repair neurons
○ If homozygous for E4, risk of Alzheimer's is much greater (90% chance by age
85)
■ Luckily Apoe4 is the least common allele
Parkinson’s Disease
● Triad:
○ Tremor
■ Pill tremor (3-5 Hz)
○ Rigidity
■ Resting tone is very high because area of the brain is affected
■ “Cogwheel” rigidity
■ Lots of stops and starts to a movement
○ Akinesia
■ Hard to initiate a movement
● Better at initiation if there is a “beat” (marching muscle)
○ Nervous system can override
● Usually no link to family history
● There are other neurological disease that have Parkinsonian features
● Changes associated Parkinson’s Disease
○ Gross
■ Pallor and atrophy of the substantia nigra
● Nucleus of dopaminergic neurons in the midbrain
● Neuron-melanin is the precursor to dopamine (give the substantia
nigra its color)
○ Micro
■ Neuronal dropout, gliosis
■ Lewy bodies (in the substantia nigra neurons) and neutires
● Accumulation and aggregation of proteins that can be degraded
● Positive for alpha-synuclein
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Document Summary
Deposit of abnormal proteins within the terminal process of neurons. Makes it difficult for axons to connect. 80% are sporadic (no identified risk factor) 3 different allelic forms (e2, e3, e4) Different version have different ability to repair neurons. If homozygous for e4, risk of alzheimer"s is much greater (90% chance by age. Luckily apoe4 is the least common allele. Resting tone is very high because area of the brain is affected. Lots of stops and starts to a movement. Better at initiation if there is a beat (marching muscle) There are other neurological disease that have parkinsonian features. Pallor and atrophy of the substantia nigra. Nucleus of dopaminergic neurons in the midbrain. Neuron-melanin is the precursor to dopamine (give the substantia nigra its color) Lewy bodies (in the substantia nigra neurons) and neutires. Accumulation and aggregation of proteins that can be degraded. Small percentages due to mutation in the synuclein gene (synuclein is a component of lewy bodies)
