Alzheimer

Question 1

causes of dementia

Answer 1

traumatic brain injury
stroke
slowly progressive dementia
rapid progressive dementia
vitamin deficiencies
hypotyroidism

Question 2

areas affected in AD

Answer 2

1. memory
2. language
3. perceptual skills
4. attention
5. constructive abilities
6. orientation
7. problem solving
8. functional abilities

tested by a MMST test

Question 3

risk factors

Answer 3

1. age
2. family history
3. genetics; risk genes increase the likelihood, but do NOT guarantee anything

Question 4

FAD, early onset familial alzheimer

Answer 4

• APP-gene on chromosome 21
• PSEN-1 on chromosome 14
• PSEN-2 on chromosome 1

Question 5

LOD, late onset alzheimer

Answer 5

• APOE gene on chromosome 19. multiple forms, e2 DECREASE in likelihood of AD
• inflammation; triggering receptor expressed on myeloid cells 2 (TREM2) gene

Question 6

Alzheimer

Answer 6

Degeneration of hippocampus (barely present)

The size of the cell bodies stay the same, the size of gray matter will NOT shrink.

Degeneration of the network, dendrites are degraded first.

Question 7

cellular hallmarks

Answer 7

• amyloid beta peptide
• hyperphosphorylation of tau
  both needed to be diagnosed

Question 8

amyloid beta peptides

Answer 8

plaques that are formed outside the cell, interferes with the communication between cells.
alpha B40/41 is the toxic form that can form fibrils.
beta-secretase cuts the toxic form, the whole block.
alpha-secretase cuts the NON-toxic form, the block through the middle.
both in combination with gamma-secretase.

Question 9

hyperphosphorylation of tau

Answer 9

happens inside the cell
forms tangles and attacks neuronal network, leading to a disabled transport system.
abnormal tau separates from the microtubules causing them to fall apart, combine to form tangles

Question 11

donepezil

Answer 11

targets cholinergic system
alzheimer’s disease

Question 12

galantamine

Answer 12

targets cholinergic system
mild to moderate AD

Question 13

rivastigmine

Answer 13

targets cholinergic system
mild to moderate AD

Question 14

memantine

Answer 14

targets other neurotransmitters, mainly glutamate; to inhibit the action of glutamate
moderate to severe AD

Question 15

leqembi

Answer 15

amyloid related target, breaking it down

Question 16

aduhelm

Answer 16

amyloid related target; breaking it down
clears plaques from brain, slows down deterioration in early AD

Question 17

brexipiprazole

Answer 17

targets other neurotransmitters
agitation/anxiety in AD

Question 18

survorexant

Answer 18

orexin receptor antagonist; promoting sleep
used for insomnia AD + mild to moderate AD

Question 19

pathology AD

Answer 19

1. amyloid beta mediated neuronal death
2. cholinergic dysfunction and NMDA inhibition
3. tau hyperphosphorylation
4. inflammation
5. clearance problems
6. cholesterol metabolism
7. insulin dysfunction
8. peripheral AB seeds

Question 20

therapy amyloid beta plaques

Answer 20

• decrease production;
  NSAIDs, rosiglitazone, semagacestat
  targeting beta and gamma secretase
• increase clearance;
  active vaccination; AB1-42 aggregates
  passive immunization; anti-AB antibodies, solanzeumab
• inhibition of aggregation;

Question 21

therapy cholinergic function and NMDA-inhibition

Answer 21

donzepil
galantamine
rivastigmine
tacrine
memantine

Question 22

therapy tau hyperphosphorylation

Answer 22

HSP90-inhibitors
autophagy enhancers
tau-kinase
O-GlcNAcase-inhibitors

Question 23

therapy inflammation

Answer 23

TNF-a by microglia released
TNF-1 receptor; induces plaque
TNF-2 receptor; neuroprotective

Question 24

therapy clearance problems

Answer 24

LRP, takes amyloid from brain to plasma > clearance
RAGE, takes amyloid from plasma to brain > no clearance

Question 25

therapy cholesterol-metabolism

Answer 25

apoE4 isoform accelerates aggregation of AB fibrils
apoE2 and E3 isoforms promote clearance of AB via LRP

Question 26

therapy insulin dysfunction

Answer 26

thiazolodines; target insulin signaling