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Flashcards in Alzheimer's disease Deck (18)
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1

Main risk factor for Alzheimer's disease

Age (also fam hx)

2

Symptoms of AD

memory loss (recent events), disorientation, confusion, language problems, personality changes = fear, anxiety, anger, poor judgment

3

3 hypotheses for AD pathophysiology

Beta-Amyloid plaques
Tau protein tangles
Inflammation

4

Normal amyloid precursor protein (APP) physiology

APP, alpha secretase, gamma secretase present in cell membrane.
alpha secretase cleaves APP, releasing sAPPa, c83 remains.
Gamma secretase cleaves c83 into other products

5

Pathological APP metabolism

APP, beta secretase and gamma secretase present in cell membrane.
Beta secretase cleaves APP to release sAPPbeta, C99 remains
Gamma secretase cleaves C99 releaseing beta amyloid, which accumulates extracellularly

6

Briefly describe Beta amyloid protein hypothesis of AD

Accumulation of beta-amyloid into EXTRAcelullar plaques due to pathophysiological metabolism of APP -> neurotoxic

7

Briefly describe Tau tangle hypothesis of AD

Hyperphosphorylated tau proteins form INTRAcellular tangles -> neurotoxic

8

Normal function of tau proteins

They SOLUBLE proteins in axon, are incorpirated into microtubule structure to stabilise them and aid assembly.

9

Pathophysiology of tau proteins in AD

Tau proteins hyperphosphorylated, become INSOLUBLE, self-aggregate producing INTRAcellular neurofibrillary tangles -> neurotoxic.
Also cause microtubule instability

10

Explain Inflammatory hypothesis of AD

Microglia produce more inflammatory mediators and cytotoxic proteins, decreased neuroprotection, increased phagocytosis

11

Normal role of microglia

Resident macrophages of the brain

12

Principle of AD drugs

Used to alleviate and improve SYMPTOMS, have no effect on pathogenicity

13

Drugs used in AD

Donepezil
Rivastigmine
Galantamine
Memantine
NB must all be able to cross BBB bc act centrally

14

Donepezil MOA + PK

reversible antiAChE, long t1/2

15

Rivastigmine MOA + PK

Pseudo-reversible antiAChE/BChE, t1/2=8hrs

16

Galantamine MOA + PK

reversible antiAChE, long t1/2, some nAChR activity

17

Memantine MOA + PK

use-dependent non-competitive NMDAR antagonist with low affinity, long t1/2

18

memantine use

for moderate-severe AD