Alzheimers

Question 1

B-Amyloid protein production occurs as a result of which enzymatic cleavage sequence?

Answer 1

B- secretase followed by G– secretase action on B-amyloid precursor protein

Question 2

APP is coded for on chromosome

Answer 2

21

Question 3

Four genetic factors have been identified that predispose to Alzheimer’s disease by affecting B- amyloid phenotype. Which of these mutations can cause increased production of all B-amyloid proteins?

Answer 3

B-amyloid precursor protein mutations (chromosome 21). Mutation at alpha cut site

Question 4

What are the three ApoE proteins and which has the best/worst efficacy at Bamyloid clearance?

Answer 4

ApoE4 = useless
ApoE3 = ok
ApoE2 = great

Question 5

What is the preferred cleavage pathway?

Answer 5

alpha, then gamma

Question 6

What is the pathogenic cleavage pathway

Answer 6

beta, then gamma

Question 7

What is the pathology of the Bamyloid protein?

Answer 7

oligomerization —> decreased synaptic efficiency –> plaque formation —-> astrocyte/microglial inflamm. response —> oxidative injury —> neuronal dysfunction/dementia

Question 8

Drug potential?

Answer 8

alpha secretase = can’t knock out. lethal

Beta secretase = ideal drug target. works great in mice. can’t find in humans