Alzheimers (Matisse)

Question 1

Dementia

Answer 1

Loss of cognitive function

• symptoms changes in personality, mood, behavior, memory loss
• irreversible (disease/injury) or reversible (drug/toxin/vitamin/depression)

Question 2

Neurodegenerative Dementias (4)

Answer 2

Alzheimer’s Disease
Frontotemporal Dementia (Picks Disease)
Lewy Body Dementia
Creutzfeld-Jakob Disease

Question 3

Dementia (mechanism, proteins for each)

Answer 3

-abnormal protein aggregation in neural tissue disrupts function
AD: Amyloid ß-42
Frontotemporal Dementia: Tau
LBD: å-synuclein
CJD: prions

Question 4

Dementia (genetics- susceptibility genes for each)

Answer 4

AD: Apolipoprotein E4
FTD: ?
LBD: Apolipoprotein E4
CJD: Prion

Question 5

Alzheimers Symptoms/progression

Answer 5

Degenerative dementia starting with recent (episodic) memory deficit- motor, alertness fine
Anosmia: early indicator
5-10yr life expectancy

Question 6

Neuritic Plaques

Answer 6

extracellular deposits of ß-amyloid protein, immune inflammatory response causes plaques since thinks it’s foreign. Constant inflammation causes neurodegeneration.

Question 7

Amyloid ß Protein production (pathway)

Answer 7

Amyloid Precursor Protein (APP) gets cleaved by å or ß secretases, then those products by gamma secretases. ß pathway produces Amyloid ß protein (Aß-42), so pro-amyloidogenic. å pathway isnt.

Question 8

ApoE4

Answer 8

this mutant form of lipoprotein predisposes risk of AD- impairs Aß-42 clearance

Question 9

Aß-42 Oligomer Toxicity Hypothesis

Answer 9

Plaques correlated with AD, but really not necessary or sufficient. Real culprit is Aß-42 oligomers that can have neurotoxic effects
-affect NMDA and Ca channels impairing signal conductance, affect cytoskeleton via LilrB2 receptor

Question 10

Neurofibrillary Tangles

Answer 10

intracellular accumulations of hyperphosphorylated Tau protein in AD, impairing proper axonal transport

• assocation with AD unclear, prob Aß downstream effect
• But Tau issue alone can be Frontotemporal Dementia

Question 11

Diagnosing AD

Answer 11

-Hx (1% AD familial)
-Mental status exam
-smell test (anosmia=early sign)
-PET amyloid scan (PIB tracer for plaques)
Aß-42 levels: low = bad since bound in plaques
Tau: high = bad since means neurodegeneration is dumping it from deteriorating cells

Question 12

AD Differential

Answer 12

Head Trauma
HIV
Huntingtons, Parkinsons, Picks (similar but motor involvement)
Vascular Dementia
Wernicke Korsakoff (alcoholism/B1 deficiency, reversible)

Question 13

AD Treatment

Answer 13

• AChesterase inhibitors (since basal ganglia affected in AD, less ACh)
• NMDA Antagonists (protect brain from glutamate excitotoxicity)

Both just treat symptoms not disease
-future stuff should target ß-secretase, Aß-42. Or antiinflammatory, antioxidants