Alzheimer's Disease Flashcards
What are the hallmarks of Alzheimer’s Disease?
Extracellular amyloid plaques (A-beta) and intracellular neurofibrillary tangles (hyperphosphorylated ptau)
What percentage of all dementias does Alzheimer’s disease account for?
60-80%
Describe an Alzheimer’s disease brain.
Decreased in size, reduced glucose usage, plaques and neurofibrillary tangles.
What is the precursor protein of amyloid plaque?
Amyloid precursor protein (APP)
There is amyloid precursor protein located?
On cell membranes
What enzyme cleaves amyloid precursor protein?
Secretase
What are the two possible products of cleavage of amyloid precursor protein?
A-beta (17-40/42, non-toxic) or A-beta (1-40/42, toxic)
Which enzymes produce the toxic A-beta (1-40/42) product of amyloid precursor protein?
Beta and gamma
Which enzymes produce the non-toxic A-beta (17-40/42) product of amyloid precursor protein?
Alpha and gamma.
What secondary structure does the A-beta protein contain?
An alpha helix.
A-beta proteins interact via which part?
Hydrophobic C-terminal end.
What is the current only approved therapy for Alzheimer’s disease?
Valsartan, an angiotensin receptor blocker.
What is the function of neurofibrillary tangles?
Stabilise microtubules. When hyperphosphorylated, they fall off and aggregate and microtubules are destabilised
How many isoforms of tau are there?
6
Which part of the tau protein associates with microtubules?
Positively charged patches R1-R4 on the C terminus and acidic groups on the N terminus.
