Alzheimers disease

Question 1

2% of the population has which gene which could make them more than 8 times more likeyl to develop AD?

Answer 1

two copes of APOE4

Question 2

0.3.5 of the population has the risk variant of …. which makes them around 3 times more likely to develop AD?

Answer 2

TREM2

Question 3

Having one copy of ….. makes people around 3 times more like to develop AD

Answer 3

APOE4

Question 4

Name some neural networls that degenerate during AD

Answer 4

1. Cholinergic basal forebrain (CBF) neurons
2. Glutamate neurons

Question 5

Name two hallmarks of AD pathology

Answer 5

1. Amyloid plaques
2. Neurofibrillary tangles

Question 6

Name secretase enyzmes in which ABeta is excised from APP (amyloid precursor protein)?

Answer 6

1. alpha-secretase
2. Beta-secretase (BACE1 and 2)
3. Gamma-secretase

Question 7

Name the 3 main approved clinical therapies for AD

Answer 7

1. Acetycholine Esterase (AChE) Inhibitor
2. NMDA Receptor Antagonists
3. Amyloid Vaccine
   Objective: enhance acetycholine action

Question 8

Which AChE inhibitor was the first anti-cholinesterase inhibitor but is rarely prescribed now due to high side effects (nausea, liver damage)?

Answer 8

Tacrine

Question 9

Which drug is used in all stages of AD and its MOA is reversible AChE inhbition?

Answer 9

Donepezil

Question 10

Which AChE drug inhibits both AChE and butrylcholinesterase?

Answer 10

Rivastigmine

Question 11

Which AChE drug is a postivie allosteric modulator of pre- and post-synaptic nicotinic ACh receptors. Increases ACh release + activity.

Answer 11

Galantamine

Question 12

Which drug interacts with Mg2+ binding site of channel to prevent excessive excitation?

Answer 12

Memantine
Also- is a weak NMDA receptor antagonist (not competitive, low affinity) and spares normal NMDA receptor function
Crosses BBB

Question 13

What is the purpose of targeting cholestrol in an attempt to treat AD?

Answer 13

Cholestrol has a direct effect on APP processing.

Question 14

What is the purpose of targeting brain metal chelation?

Answer 14

ABeta aggregation is partly dependent on the metal ions Cu2+ and Zn2+. Clioquinol -> antifungal/protozoan/viral agent. Chelates Cu2+/Zn2+ -> anti-amyloidogenic

Question 15

What is the purpose of using NSAIDSs for AD treatment?

Answer 15

Anti-inflammatory drugs may help to alleviate excessiver microglial activation in response to the accumulation of ABeta.