Ch. 6 Neurodegenerative Diseases

Question 1

What is Alzheimer’s?

Answer 1

most common form of dementia - progressive mental deterioration | begins after 60y/o, risk increases w/ age; death w/in 5-10yrs from onset

Question 2

What is beta-amyloid?

Answer 2

sticky protein fragment that clumps together in the brain –> disrupt healthy tissue –> can be inflammatory

Question 3

What is the function of APOE gene?

Answer 3

encodes for a protein involved in determining the structure and function of fatty membrane surrounding brain cell

Question 4

What is the definitive way to diagnose AD?

Answer 4

examine brain tissue post-mortem for plaques and tangles

Question 5

What are the 2 forms of AD and which is more common?

Answer 5

familial (before 65y/o)

sporadic (after 65 y/o) = most common

Question 6

What are the associated chromosomes of both forms of AD?

Answer 6

familial = Chromosomes 1,14, 21

sporadic = chromsome 19

Question 7

What are the genes associated with familial AD?

Answer 7

genes that influence beta-amyloid production

Question 8

What are the genes associated with sporadic AD? Which allele is a risk factor?

Answer 8

APOE e2, APOE e3, APOE e4

having 1 APOE e4 allele increases risk BUT does NOT determine expressivity

Question 9

What is the mechanism of disease of Alzheimer’s disease?

Answer 9

loss of cholinergic neurons in certain parts of brain –> formation of beta-amyloid plaques and neurofibrillary tangles in neurons

Question 10

What is the inheritance pattern of familial AD?

Answer 10

autosomal dominant

Question 11

What is the common clinical feature of AD?

Answer 11

impaired intellectual function –> short term memory loss; aphasia, apraxia, agnosia

Question 12

What are early symptoms of AD?

Answer 12

problems with memory and visuospatial capabilities

Question 13

What are signs and symptoms of AD progression?

Answer 13

personality changes, behavioral difficulties, hallucinations

Question 14

What are the 6 signs and symptoms of end-stage AD?

Answer 14

• 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

Question 15

What are the 4 risk factors for AD?

Answer 15

• greater age
• family hx
• lower education level
• female gender

Question 16

What are the 3 testing/screening techniques used for AD?

Answer 16

• neuro-imaging
• family and medical hx
• lab tests
• mini mental exam

Question 17

What are 3 treatments for AD?

Answer 17

mild-moderate AD = acetylcholinesterase inhibitor

moderate-severe AD = memantine

BOTH improve cognitive function

• Aducanumab (A-beta monoclonal Ab) = showed ↓ in plaques and tau proteins

Question 18

What is Huntington’s Disease (HD)?

Answer 18

fatal, progressive neuro-degenerative disease impacting nerve cells in the brain

not reversible; death w/in 15yrs from onset

Question 19

What characterizes HD?

Answer 19

involuntary movements of all body parts; cognitive function deterioration; severe emotional disturbance

Question 20

What inheritance pattern is HD?

Answer 20

autosomal dominant

Question 21

What inheritance pattern is AD?

Answer 21

autosomal dominant w/ complete dominance

Question 22

What is the pathology of HD?

Answer 22

microscopic deposits of amyloid-related protein in basal ganglia

Question 23

What is the risk factor for HD?

Answer 23

Caucasians w/ northwestern European ancestry

Question 24

What does computerized tomography scanning provide when testing for HD?

Answer 24

shows cerebral and/or caudate nucleus atrophy

Question 25

What are the 7 mechanisms of pathogenesis in Huntington’s disease?

Answer 25

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

Question 26

What are the 7 pathologies of Alzheimer’s disease?

Answer 26

• striatum (neuronal cell death)
• brain shrinkage
• dementia
• vasopressin overproduction
• weight loss
• muscular atrophy
• cardiac failure

Question 27

How does vasopressin play a role in pathology of AD?

Answer 27

regulates water processing in body –> affects blood pressure

can lead to cardiac failure

Question 28

What causes the neurofibrillary tangles of AD?

Answer 28

tau protein