AD

Question 1

causes of AD

Answer 1

synapses
prenatal infections
immune system
aging parents, pesticides
GI tract

Question 2

Cells involved in neuroinflammation in AD

Answer 2

Microglia
Myeloid cells other than resident microglia
Astrocytes
Other CNS cells

Question 3

AD as a neurodegen and neuroinflamm. disease

Answer 3

Neuroinflamm: Tissue invasion by blood derived immune cells eg T and B cells
Neurodegen: Innate immune response eg macrophages and microglia

Question 4

How do microglia and AB monomers interact

Answer 4

AB monomers bind to microglia which leads to a downregulation in phagocytic capacity therefore more AB accumulates

Question 5

Explain AB clearance by microglia

Answer 5

1. Receptor mediated phagocytosis in vitro

2. Extracellular proteases eg neprilysin and insulin degrading enzyme

Question 6

Define myeloid cells

Answer 6

Non microglial myeloid cells- meningeal and choroid plexus

Perivascular macrophages - removal of AB

Question 7

How do astrocytes promotte neuroinflammation

Answer 7

Astrocytes undergo atrophy that preceeds AB clearance hence less phagocytosis of AB

Question 8

Which cells respond to pathological stimuli via reactive gliosis?

Answer 8

astrocytes, they are locatetd near plaques and take up and degrade A beta

Question 9

Oligos and Neurons in neuroinf.

Answer 9

Oligos express complement components and chemokines

Neurons express complement proteins

Question 10

Common targets of AD therapies

Answer 10

BACe inhibitor,
prevent monomers from forming oligomers
prevent oligomers from forming fibrils
clear fibrils

Question 11

Why are most AD targets not promising?

Answer 11

Improper modellign organisms eg APP mouse has only one pathology
Disorder of age eg using 13 month old mice
Pathophysiology still not understood
Diagnosis is late

Question 12

Markers in AD
Microglial processes
Phagosomes
Fibrils
Plaques

Answer 12

Microglial processes- Iba1
Phagosomes- CD68
Fibrils-4G8
Plaques-Thioflavin s

Question 13

Loss of microglia barrier function leads to decreased AB fibril compaction and greatest impact on axonal dystrophy . True / flase

Answer 13

true. Loss of microglia barrier function leads to decreased AB fibril compaction and greatest impact on axonal dystrophy .

Question 14

3 components of inflammasomes

Answer 14

1. Nod like receptor 3
2. Eruptor molecule ASC
3. Procaspase 1 attaches to ASC

Question 15

Which receptor mediates interaction of microglia and AB plaques

Answer 15

TREM2 receptor

Question 16

NLRP3 Inflammasome pathway activation and IL1β production in AD contributes to
disease pathology. T/F

Answer 16

True. Pharmacological targetting of the NLRP3 pathway leads to improved cognitive
function and reduced plaques in APP/PS1 mice (AD mice model).

Question 17

What is responsible for early synaptic loss in AD

Answer 17

Complement sys and microglia activation. Dysfunctional microglia could itself lead to disease relevant phenotype.

Question 18

Glial cells provide new therapeutic targets to curb the early progression of AD or other
neurodegnerative disorders

Answer 18

True

Question 19

2 pathways in AD

Answer 19

amyloidogenic beta and gamma secretase

non-amyloidogenic alpha and gamma secretase