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Flashcards in 14 - AD Deck (22):
1

AD: definition?

age dependent GLOBAL deterioration of intellectual + cognitive function

2

AD: symptoms + signs

impaired: memory, attention, language, communication, abstract thinking, judgement, personality, depression, visuo-spatial disorientation. motor + gait disturbances, extrapyramidal signs, bladder/bowel control problems.

3

4 things to diagnose AD?

history of symptoms + exam. tests to exclude other causes of dementia. brain imaging with CT, MRI. other brain tests like MRI diffusion tensor imaging, PET scans, detection of amyloid

4

AD: % cause of dementia? % cost?

most common cause, 70 - 80% of dementia. 40% total health care cost associated with neuological diseases

5

AD: % people? # people?

7 - 9% canadian population over 65 and 35.5% over 85 have AD. 4.5 million people in can/US, will be 14 million by 2050

6

2 main types of AD? associated genes?

early onset: APP, Presenilin 1 and 2. late (over 65) Apo E

7

PS1 and PS2: what? KO mice?

integral membrane proteins with 8 TM domains. double KO of PS1 = decrease in protein Notch important for embryogenesis and neural development, also decreased AB 1 - 40 and 1 - 42 development

8

presenilin 1 and 2: implicated as?

the enzyme responsible for Y-secretase cleavage of APP

9

4 Apo E functions in CNS

transport of cholesterol, phospholipids, fatty acids + anti-oxidant vitamins in serum/CSF. synaptic remodelling and regeneration. interacts with amyloid metabolism. interacts with cytoskeleton

10

number of apo E 4 copies affects (4)?

risk of developing AD. age of onset. accumulation of brain markers of AD like amyloid plaque and NFT load. neuronal cell number/density in hippocampus.

11

apo E 4 and age on onset?

decreases age of onset of AD. no apoe E 4 = late onset. 2 alleles = earlier onset

12

apo E 4 and response to ChEI?

cortical cholinergic dysfunction: ApoE4 positive has worst cholinomimetic drug response, ApoE 4 negative has best response

13

cholinergic basal forebrain nuclei project to? lesions? AD?

CFB nuclei project to hippocampus + limbic areas. lesions in CBF = impairs learning and memory. degeneration of these neurons important in AD.

14

memantine: does what?

treats symptoms at all stages of AD, not a cure. interferes with release of too much glutamate.

15

4 neuropathological features of AD

cortical atrophy, especially of temporal + parietal cortices. NFTs. senile amyloid plaques. granulovacuolar degeneration and hirano bodies.

16

processing of APP

a secretase = soluble APP, good guy. B + Y secretase = aggregated AB and CT fragment = bad, neurotoxic

17

glutamate cell death and amyloid?

glutamate induced cell death potentiated by amyloid; potentiates toxic effect

18

apoE4 knock IN mice show? AD patients? concl about ApoE4 and AD?

decrease in GABA interneurons. learning/memory deficits. AD pts: decreased GABA = apoE4 contributes to AD partially by causing impairments of GABA interneurons.

19

3 potential therapeutic strategies for AB?

lower AB production w/ secretase inhibitors, enhance AB clearance w/ antibodies or enzymes. block interaction of AB with cell surface receptors. modulate downstream pathways.

20

AB binds to what receptors?

nAChRs : a7 and a4b2 subtypes. may have multiple receptor targets

21

6 protective factors for AD

high education. NSAIDs. statins (lower cholesterol). red wine. intellectual leisure activities and socialization. post menopausal hormone replacement therapy

22

possible AD treatments

ACh: inhibit esterases, muscarinic/nitotinic bifunitonals. beta-amyloid: APP-releasers, anti-aggregation agents. also: estrogen, anti-oxidants, anti inflammatories, free radical scavengers