The Healthy Brain

Question 1

What are pathological hallmarks of Alzheimer’s?

Answer 1

-extracellular: Amyloid plaques (Abeta) on blood vessels
-intracellular: neurofibrillary tangles (TAU)

Question 2

What happens to synapses in Alzheimer’s?

Answer 2

In early AD there is extensive synapse loss.
Eg: 44% of dentate gyrus and 51% of CA1 hippocampus

Question 3

What pathways does the Amyloid precursor protein (APP) have during metabolism?

Answer 3

Beta-cleavage and Alpha cleavage

Question 4

What is Beta cleavage of amyloid precursor protein (APP)?

Answer 4

Leads to production of ABeta which is cleaved releasing into body- amyloidgenic pathway

Question 5

What is the alpha cleavage of Amyloid precursor protein?

Answer 5

Leads to production of P3 when gamma cleavage occurs: non-amyloidgenic

Question 6

What is an amyloidgenic pathway?

Answer 6

A pathway that produces neurotoxic AB

Question 7

What causes increased concentration of amyloid beta in the brain?

Answer 7

Mutations found in APP and PS1

Question 8

What can protect you from Alzheimer’s?

Answer 8

A mutation in APP called A637T. 1/100 Icelanders have it.

Question 9

What does A637T cause?

Answer 9

A637T reduces BACE1 cleavage of APP (B-cleavage) resulting in lower AB secretion.