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M2M1 > Alzheimer's > Flashcards

Alzheimer's Flashcards

1
Q

Common mechanism of action…alz?

A

Increase ab42

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2
Q

Where does ab42 come from?

A

b-amyloid precursor protein APP

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3
Q

What is APP?

A

A large ubiquitously produced protein in mammalian cells - transmembrane protein - and processed by several possible enzymatic cleavages

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4
Q

Possible extracellular cleavages of APP

A

alpha secretase

beta secretase

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5
Q

Transmembrane cleavage of APP

A

gamma secretase

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6
Q

Where does AB42 come from?

A

beta secretase –> gamma secretase

action on beta amyloid precursor protein (APP)

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7
Q

APP processing… what is favored pathway?

A

alpha secretase –> gamma secretase

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8
Q

APP processing,…what pathway leads to AB40 and AB42?

A

beta secretase –> gamma secretase

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9
Q

4 mutations that lead to increased AB42?

A 
Chromosome 21 (app)
Chromosome 14 (presenilin 1)
Chromosome 1 (presenilin 2)
Apolipoprotein E4 polymorphism (chormosome 19) -- via decreased clearance
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10
Q

Mutated gamma secretase increases?

A

AB42 production

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11
Q

Four genetic factors have been identified that predispose to alzheimer’s by affecting beta amyloid phenotype. Which of these mutations acts by increasing the production of ALL beta amyloid proteins?

A

APP mutations (chromosome 21)

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12
Q

Cause of ApoE e4 Alz manifestation?

A

Decreased AB clearance

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13
Q

Potential interventions

How could we reduce production of AB42?

A

Modulate secretase activity

Disrupt beta secretase in some way?

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14
Q

Potential interventions

How could we increase AB42 clearance?

A

Cholesterol/statins?

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15
Q

Potential interventions

How could we decrease AB42 toxicity?

A

Decrease oligimerization / protect mitochondria?

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16
Q

Potential interventions

How could we decrease oxidative injury?

A

Chelate divalent metals?

17
Q

Potential interventions

How could we decrease inflammatory response?

A

NSAIDS, steroids

18
Q

Potential interventions

How could we decrease damage to nuerons?

A

memantine

19
Q

Potential interventions

How could we compensate for neuronal dysfunction

A

Donepezil

20
Q

How could we decrease production of AB42 by modulating secretase activity?

A

Decrease beta secretase

Decrease gamma secretase

21
Q

What does presenilin 1 code for?

A

gamma secretase (maybe)

22
Q

How could we increase AB clearance?

A

Somehow use ApoE dependent clearance?

23
Q

ApoE4 (+) increased risk?

A

15–>29%

24
Q

ApoE4 (-) decreased risk?

A

15–>9%

25
Q

Protective allele?

A

ApoE2

26
Q

Risk factors outside genetics?

A 
Hypertension
diabetes
smoking 
cholesterol 
obseity
27
Q

Prevention

A

Move and weight train :)

28
Q

Tau

A

Protein involved in nuerofibrillary tangles

M2M1 (7 decks)

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