Alzheimer's Disease

Question 1

What are the physiological roles of astrocytes?

Answer 1

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

Question 2

What are the physiological roles of oligodendrocytes?

Answer 2

Insulate axons with myelin - increase AP conduction speed

Question 3

What are the physiological roles of microglia?

Answer 3

Resident immune cells

Clear debris and dead cells

Question 4

Name the top 3 neurodegenerative diseases

Answer 4

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

Question 5

What are the main symptoms of AD?

Answer 5

Short term memory loss
Confusion
Language difficulty

Question 6

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

Answer 6

Women - AD

Men - CVD

Question 7

How are global AD rates changing and why?

Answer 7

Increasing

As increasing life expectancy

Question 8

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

Answer 8

LMICs

Largest projected increase in life expectancy

Question 9

Which enzymes cleave APP to form AB?

Answer 9

Beta- then gamma-secretase

Question 10

Which familial AD genes are linked to AB formation?

Answer 10

APP
PSEN1
PSEN2

Question 11

What is the largest AD risk factor?

Answer 11

Age

Question 12

What are the stages of AD development?

Answer 12

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

Question 13

What are the common pathways in ageing and AD?

Answer 13

Nutrient pathways
Autophagy and proteasome - proteostasis
Inflammation

Question 14

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

Answer 14

Impaired

Question 15

What drives inflammageing?

Answer 15

Increased microglia

Question 16

What is the second largest AD risk factor?

Answer 16

T2D

Question 17

How does insulin resistance affect cognitive decline?

Answer 17

Increases

Question 18

How is glucose metabolism altered in AD?

Answer 18

Decreased

Question 19

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

Answer 19

Improves symptoms

Question 20

What is the evidence for impaired autophagy in AD?

Answer 20

Autophagosome accumulation

Question 21

What is the evidence for impaired UPS in AD?

Answer 21

Decreased proteasome degradation efficiency

Increased ubiquitinated aggregates

Question 22

How can AB and tau affect UPS?

Answer 22

Inhibit proteasome

Question 23

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

Answer 23

TREM2

CD33

Question 24

What is the effect of prolonged microglial activation?

Answer 24

Neuronal damage

Question 25

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

Answer 25

Increased paralysis with ageing | AB expression increases paralysis likelihood

Question 26

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

Answer 26

Slight decrease in climbing ability with ageing | AB expression in adult neurons only - further decreases climbing ability

Question 27

What is the effect of AB expression in mouse brains?

Answer 27

Worsens Morris watermaze performance - impaired learning and memory

Question 28

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

Answer 28

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

Question 29

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

Answer 29

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

Question 30

How does metformin act?

Answer 30

Activates AMPK

Question 31

What is the effect of metformin on WT animals?

Answer 31

Extends lifespan

Question 32

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

Answer 32

Improves climbing | AMPK activation improves AB pathology

Question 33

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

Answer 33

No improvement to climbing ability | DR extends lifespan but does not affect AB pathology

Question 34

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

Answer 34

Modulating age-related pathways affects AD development