Ch. 6 Neurodegenerative Diseases Flashcards
What is Alzheimer’s?
most common form of dementia - progressive mental deterioration | begins after 60y/o, risk increases w/ age; death w/in 5-10yrs from onset
What is beta-amyloid?
sticky protein fragment that clumps together in the brain –> disrupt healthy tissue –> can be inflammatory
What is the function of APOE gene?
encodes for a protein involved in determining the structure and function of fatty membrane surrounding brain cell
What is the definitive way to diagnose AD?
examine brain tissue post-mortem for plaques and tangles
What are the 2 forms of AD and which is more common?
familial (before 65y/o)
sporadic (after 65 y/o) = most common
What are the associated chromosomes of both forms of AD?
familial = Chromosomes 1,14, 21
sporadic = chromsome 19
What are the genes associated with familial AD?
genes that influence beta-amyloid production
What are the genes associated with sporadic AD? Which allele is a risk factor?
APOE e2, APOE e3, APOE e4
having 1 APOE e4 allele increases risk BUT does NOT determine expressivity
What is the mechanism of disease of Alzheimer’s disease?
loss of cholinergic neurons in certain parts of brain –> formation of beta-amyloid plaques and neurofibrillary tangles in neurons
What is the inheritance pattern of familial AD?
autosomal dominant
What is the common clinical feature of AD?
impaired intellectual function –> short term memory loss; aphasia, apraxia, agnosia
What are early symptoms of AD?
problems with memory and visuospatial capabilities
What are signs and symptoms of AD progression?
personality changes, behavioral difficulties, hallucinations
What are the 6 signs and symptoms of end-stage AD?
- near mutism
- inability to sit up or hold head
- inability to swallow or eat = weight loss
- bowel/bladder incontinence
- inability to track with eyes - recurrent respiratory or urinary infections
What are the 4 risk factors for AD?
- greater age
- family hx
- lower education level
- female gender
What are the 3 testing/screening techniques used for AD?
- neuro-imaging
- family and medical hx
- lab tests
- mini mental exam
What are 3 treatments for AD?
mild-moderate AD = acetylcholinesterase inhibitor
moderate-severe AD = memantine
BOTH improve cognitive function
- Aducanumab (A-beta monoclonal Ab) = showed ↓ in plaques and tau proteins
What is Huntington’s Disease (HD)?
fatal, progressive neuro-degenerative disease impacting nerve cells in the brain
not reversible; death w/in 15yrs from onset
What characterizes HD?
involuntary movements of all body parts; cognitive function deterioration; severe emotional disturbance
What inheritance pattern is HD?
autosomal dominant
What inheritance pattern is AD?
autosomal dominant w/ complete dominance
What is the pathology of HD?
microscopic deposits of amyloid-related protein in basal ganglia
What is the risk factor for HD?
Caucasians w/ northwestern European ancestry
What does computerized tomography scanning provide when testing for HD?
shows cerebral and/or caudate nucleus atrophy
What are the 7 mechanisms of pathogenesis in Huntington’s disease?
A - Aggregate formation: proteins clumping up and not folding properly = disrupts how the cell functions/communicates
T - Transcriptional dysfunction: genes turning on/off inappropriately; chromatin modification
A - Altered protein homeostasis: proteasome dysfunction, altered process/regulation of proteins
M - Mitochondrial dysfunction: defective Ca2+ homeostasis = ion imbalance –> ↓ATP production;
ROS (reactive oxygen species) interrupts exchange of electrons –> can lead to inflammation
S - altered Synaptic plasticity: excitotoxicity
A - Axonal transport defect: impaired organelles of delivery system
N - Neuroglia dysfunction: microglia = secrete messages = over-trigger of inflammation = can lead to cell death;
Astrocytes = not taking up glutamate as much
What are the 7 pathologies of Alzheimer’s disease?
- striatum (neuronal cell death)
- brain shrinkage
- dementia
- vasopressin overproduction
- weight loss
- muscular atrophy
- cardiac failure
How does vasopressin play a role in pathology of AD?
regulates water processing in body –> affects blood pressure
can lead to cardiac failure
What causes the neurofibrillary tangles of AD?
tau protein
