Alzheimer's disease

Question 1

What are the clinical symptoms of AD?

Answer 1

memory loss
disorientation/confusion
language problems
personality change
poor judgement

Question 2

What are the risk factors?

Answer 2

Age (main)

genetics –> APP, PSEN + ApoE

Question 3

What is the B-amyloid hypothesis?

Answer 3

Amyloid precursor protein (APP) cleaved by b-secretase –> sAPPB released –> C99 fragment remains –> C99 digested by y-secretase –> releases B amyloid protein –> form toxic aggregates

Question 4

How does vascular dementia occur?

Answer 4

B-amyloid plaques –> attach to blood vessels

Question 5

What are Tau proteins?

Answer 5

soluble proteins present in axons

important in microtuble assembly + stability

Question 6

What is the Tau hypothesis?

Answer 6

hyperphosphorylated Tau proteins –> self aggregates to form tangles –> neurotoxic –> also result in microtubule instability –> breakdown –> degeneration

Question 7

What is the inflammation hypothesis?

Answer 7

inappropriate activation of microglial cells –> increased release of inflammatory mediators etc + decreased levels of neuroprotective protein

Question 8

What are the four drugs licenced for AD in the UK + some of their key characteristics?

Answer 8

3x cholinesterases:
- Donepezil
- Rivastigmine (patch, also inhibits BChE)
- Galantamine (additional nAChR properties)
1x NMDA blocker:
- Memantine (only used in late stage)

Question 9

What are some AD treatment failures?

Answer 9

y-secretase inhibitors
B-amyloid treatments
Tau inhibitors