Alzheimer's disease

Question 1

Which are the 2 hallmarks of alzheimer’s disease?

Answer 1

1. Extracellular amyloid beta plaques.

2. Intracellular neurofibrillary tangles (tau).

Question 2

Name 3 acetylcholinesterase inhibitors used to reat Alzheimer’s.

Answer 2

Donepezil, galantamine & rivastigmine.

Question 3

Name a NMDA receptor antagonist.

Answer 3

Memantine.

Question 4

Explain the cholinergic hypothesis.

Answer 4

Decline in acetylcholine signalling in cholinergic neurones.

Question 5

Explain the excitotoxicity hypothesis.

Answer 5

NMDA receptor activated by glutamate - Ca2+ influx. Glia cells take up glutamate and deliver it as glutamine to neurons. In AD excess glutamate due to poor reuptake - excessive Ca2+ influx - free radicals - inflammatory mediators - toxicity.

Question 6

Explain the oxidative stress hypothesis.

Answer 6

Excess production of free radicals leading to inflammation and cell damage.

Question 7

Explain the ApoE hypothesis.

Answer 7

ApoE e2 & 4 variants increase amyloid beta aggregation, reduces amyloid beta clearance.

Question 8

Explain the GSK3 hypothesis.

Answer 8

GSK3 - glycogen synthase kinase 3 - isoform beta is crucial for tau hyperphosphorylation, important for amyloid beta aggregation and disposition, links to neuroinflammation and oxidative stress.

Question 9

Explain the inflammation hypothesis.

Answer 9

Patients on anti-inflammatory treatment for e.g. rheumatoid arthritis have lower risk of AD. Focuses on reducing systemic inflammation.

Question 10

Name the current treatment strategies on clinical trials.

Answer 10

Anti-amyloid beta, anti-neuroinflammation, anti-tau, neuroprotection, cognitive enhancers, BPSD relieving therapy.