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BIOL0027 > Alzheimer's Disease > Flashcards

Alzheimer's Disease Flashcards

1
Q

What are the physiological roles of astrocytes?

A

Provide nutrients for neurons
Digest parts of dead/excess neurons
Regulate neuronal firing - NT uptake

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2
Q

What are the physiological roles of oligodendrocytes?

A

Insulate axons with myelin - increase AP conduction speed

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3
Q

What are the physiological roles of microglia?

A

Resident immune cells

Clear debris and dead cells

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4
Q

Name the top 3 neurodegenerative diseases

A

1st - stroke
2nd - AD
3rd - PD

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5
Q

What are the main symptoms of AD?

A

Short term memory loss
Confusion
Language difficulty

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6
Q

What are the leading causes of death for men and women in the UK?

A

Women - AD

Men - CVD

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7
Q

How are global AD rates changing and why?

A

Increasing

As increasing life expectancy

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8
Q

Where is the largest increase in AD rates expected and why?

A

LMICs

Largest projected increase in life expectancy

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9
Q

Which enzymes cleave APP to form AB?

A

Beta- then gamma-secretase

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10
Q

Which familial AD genes are linked to AB formation?

A

APP
PSEN1
PSEN2

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11
Q

What is the largest AD risk factor?

A

Age

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12
Q

What are the stages of AD development?

A

AB plaques -> tau tangles -> brain structure changes -> memory impairment

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13
Q

What are the common pathways in ageing and AD?

A

Nutrient pathways
Autophagy and proteasome - proteostasis
Inflammation

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14
Q

How is autophagy and proteasome function altered in both ageing and AD?

A

Impaired

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15
Q

What drives inflammageing?

A

Increased microglia

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16
Q

What is the second largest AD risk factor?

A

T2D

17
Q

How does insulin resistance affect cognitive decline?

A

Increases

18
Q

How is glucose metabolism altered in AD?

A

Decreased

19
Q

What is the effect of upregulating glucose metabolism in a Drosophila AD model?

A

Improves symptoms

20
Q

What is the evidence for impaired autophagy in AD?

A

Autophagosome accumulation

21
Q

What is the evidence for impaired UPS in AD?

A

Decreased proteasome degradation efficiency

Increased ubiquitinated aggregates

22
Q

How can AB and tau affect UPS?

A

Inhibit proteasome

23
Q

Which common AD risk variants are involved in inflammation and microglia?

A

TREM2

CD33

24
Q

What is the effect of prolonged microglial activation?

A

Neuronal damage

25
Q

What is the key feature of C. elegans AD model and how does this compare to WT ageing?

A

Increased paralysis with ageing

AB expression increases paralysis likelihood

26
Q

What is the key feature of Drosophila AD model and how does this compare to WT ageing?

A

Slight decrease in climbing ability with ageing

AB expression in adult neurons only - further decreases climbing ability

27
Q

What is the effect of AB expression in mouse brains?

A

Worsens Morris watermaze performance - impaired learning and memory

28
Q

What is the effect of crossing an AB-expressing mouse with an IGF receptor mutant (decreased insulin signalling) mouse and what does this suggest?

A

Offspring had better Morris watermaze performance than AB-expressing - but lower than WT
Decreasing insulin signalling increases learning ability

29
Q

What is the effect of crossing an APP mutant mouse with an mTOR KO mouse and what does this suggest?

A

Offspring had improved Morris watermaze performance - to same level as WT
TOR deletion increases learning

30
Q

How does metformin act?

A

Activates AMPK

31
Q

What is the effect of metformin on WT animals?

A

Extends lifespan

32
Q

What is the effect of metformin in AB-expressing Drosophila and what does this suggest?

A

Improves climbing

AMPK activation improves AB pathology

33
Q

What is the effect of dietary restriction on AB-expressing Drosophila and what does this suggest?

A

No improvement to climbing ability

DR extends lifespan but does not affect AB pathology

34
Q

What is the key point for the idea that age causes AD and the incidence increase is not just an effect of time?

A

Modulating age-related pathways affects AD development

BIOL0027 (20 decks)

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