Alzheimer's disease

Question 1

What are the main symptoms of AD?

Answer 1

Memory loss- most recent in particular
Dysfunction/confusion
Language problems
Personality change
Poor judgement

Question 2

Describe the amyloid hypothesis

Answer 2

In pathophysiology: amyloid precursor protein is cleaved by beta secretase. C99 fragment is cleaved by gamma-secretase and results in beta-amyloid protein released.
Beta amyloid protein forms fibrils and deposits extracellular on neuronal cells to form aggregates/plaques.

Question 3

Describe the tau hypothesis

Answer 3

In pathophysiology; tau protein is hyperphosphorylated.
It then dissociates from the microtubules and self-aggregates intracellularly which is neurotoxic.
Also, contributes to microtubule instability.

Question 4

What is the inflammatory hypothesis?

Answer 4

Increased activation of microglial cells leads to;
increased production of inflammatory mediators and cytokineproteins
increased phagocytosis
decreased levels of neuroprotective proteins

Question 5

What are the drugs used in treatment of mild-moderate AD?

Answer 5

Anticholinesterases;
Donepezil- reversible, long plasma half life

Rivastigmine-pseudo-revesible AChE and BChE inhibitor, 8 hr half-life, made into transdermal patch

Galantamine- reversible, 7-8 hr half life, a7 nAChr agonist (stimulate more secondary messenger pathways)

Question 6

What are the drugs used in treatment of moderate-severe AD?

Answer 6

NMDA receptor blockers

Memantamine- use dependent, non-competitive NMDA receptor blocker with low affinity. Long plasma half life.