Alzheimers Progression

Question 1

What are 3 factors of the AD neuropathological profile?

Answer 1

Amyloid beta plaques
Neurofibrillary tangles & neuropil threads
tau protein

Question 2

What are 2 cases of AD?

Answer 2

Familial (RARE)
Sporadic

Question 3

What is AD termed late onset?

Answer 3

After 65 years of age

Question 4

What are 4 risk factors for sporadic AD?

Answer 4

Ageing
sex (2/3 women)
genetic variants
immunobiography

Question 5

What 3 genes are mutated in sporadic AD?

Answer 5

Presenilin gene 1 & 2
amyloid precursor protein
Apolipoprotein E

Question 6

What 2 chromosomes is the presenilin gene located on?

Answer 6

1 and 14

Question 7

What chromosome is APP gene located on/

Answer 7

21

Question 8

What chromosome is APOE gene located on?

Answer 8

19

Question 9

What other neurological disorder can generate early onset AD and why?

Answer 9

Individuals with down syndrome (trisomy 21)

Question 10

What are 4 other egentic factors?

Answer 10

ATP binding cassette transporter A1
Clusterin gene
Bridging Integrator 1
ECSIT

Question 11

What does APP produce?

Answer 11

C-terminal fragments under hyrdolysis of secretases by 3 pathways

Question 12

What is the amyloid cascade hypothesis?

Answer 12

Deposition of amyloid-beta in the brain initiates AD pathogenesis leading to tau deposition, neuron & synaptic loss and cognitive decline

Question 13

What cleaves APP?

Answer 13

beta secretase

Question 14

What is the function of tau?

Answer 14

Maintains microtubule structure & cytoplasmic transport function, maintain synaptic structure & function & regulate neuronal signalling

Question 15

What is the tau hypothesis?

Answer 15

Elevated tau-tau interactions & polymerization form NFTs which cause neurotoxicity and reduce synapses

Question 16

What is the CV hypothesis?

Answer 16

Amyloid beta reduces cerebral blood flow which promotes amyloid beta production

Question 17

Where is APOE mainly expressed/

Answer 17

Astrocytes

Question 18

What is the pathophyisology of APOE?

Answer 18

Enhance amyloid deposition
Impedes Amyloid beta clearance
increased microgliosis
enhanced neuroinflammatory cytokine release

Question 19

What are 2 infections that can lead to inflammation of the brain and cause AD?

Answer 19

Human herpes virus
Porphyromomas gingivalis

Question 21

What does HHV-6 increase in the brain?

Answer 21

Amyloid beta precipitation & neuronal loss

Question 22

What does P. gingivalis cause?

Answer 22

Activation of the complement pathway in the brain -> neuroinflammation

Question 23

What does intracerebral infection lead to?

Answer 23

Induce Abeta fibrillization as an antimicrobial defence mechanisms

Question 24

What do chronic infections cause?

Answer 24

Accumulation of amyloid plaques & NFT

Question 25

What does HSV-1 cause in the brain?

Answer 25

Activation of the inflammatory response

Question 26

What 2 neuroimmune activations are prominent in AD?

Answer 26

Reactive astrogliosis microgliosis

Question 27

What are SNPs thought to be involved in?

Answer 27

Microglial function

Question 28

What 8 immune-related SNPs involved in AD?

Answer 28

TREM2 CR1 SHIP1 BIN1 CD33 PICALM CLU MSA4

Question 29

What endocrine disorder is related to AD?

Answer 29

T2DM

Question 30

What is the role g=of glucagon-like peptide 1?

Answer 30

Normalizes insulin signalling & is involved in neuronal activites & brain functions

Question 31

what happens if there is a lack of GLP-1 receptors?

Answer 31

Affects synaptic plasticity & cognitive processes

Question 32

What are 4 steps of T2DM that lead to AD?

Answer 32

1. high free fatty acids 2. BBB permeabilization 3. Glial-mediated brain inflammation 4. neuronal insulin resistance, ER-stress, synaptic failure