Microglia in AD- Rahman Flashcards
Which of the following statements about AD is/are wrong?
a. AD is a progressive neuroinflammatory disease
b. AD is a neurodegenerative disease
c. AD is characterised by Aß plaques and p-tau tangles
d. AD starts starts at many different regions in the brain at once
e. AD is the most common cause of dementia in old adults
f. all of the above are correct
d. AD starts starts at many different regions in the brain at once
–> AD starts at a specific region and spreads to other regions due to Aß aggregation
T/F
the cause of AD is unknown, however the APP processing mechanism is known to be involved. This mechanism is impaired in AD, and instead of separation of APP into sAPP-beta and APP-CTF 99 by the enzyme beta- secretase, APP is cut into sAPP-alpha and APP-CTF 83 by the enzyme alpha secretase.
These molecules are then processed again by the enzyme gamma-secretase but because of the wrong educts, the products of the process are Aß and AICD
FALSE!
Correct answer:
The cause of AD is unknown, however the APP processing mechanism is known to be involved.
This mechanism is impaired in AD, and instead of separation of APP into sAPP-alpha and APP-CTF 83 by the enzyme alpha secretase (non-amyloidogenic PW), APP is cut into into sAPP-beta and APP-CTF 99 by the enzyme beta- secretase (Amyloidogenic PW).
These molecules are then processed again by the enzyme gamma-secretase (involved in both PWs) but because of the wrong educts, the products of the process are Aß and AICD
what are the 3 therapeutic approaches for AD?
- prevent oligomer formation
- prevent fibril fragmentation and propagation
- prevent secondary nucleation
AD therapy is limited because…(choose the WRONG answer)
a. diagnosis of the disease is too late
b. improper model organisms (most MO have only 1 aspect of the disease, and AD is a very multifaceted disorder)
c. pathophysiology of the disease is still largely unknown
d. mice used in AD-research are too old and die in the middle of the study
d. mice used in AD-research are too old and die in the middle of the study
–> correct answer: mice used in AD research are not old enough in comparison to aged humans who suffer from the disease (AD is a disease of age)
disease associated microglia have been linked to AD, and are characterised by…
a. defective proteostasis
b. relaese anti-inflammatory cytokines
c. release reactive oxygen species and NO
d. unnecessary priming of resting microglia
e. all of the above
a, c, d
a. defective proteostasis
c. release reactive oxygen species and NO
d. unnecessary priming of resting microglia
How does TREM2 receptor mediate the interaction of MG and Aß-plaques?
a. Aß binds to TREM2 and this complex activates MG and reduce phagocytic capacity of MG against Aß-plaques
b. TREM2 binds to MG and activates it when not necessary
c. Aß binds to MG at the TREM2 receptor and acts as a TREM2 antagonist, preventing MG from binding TREM protein thereby
d. there is no consensus about the mechanism of MG activation in AD
a. Aß binds to TREM2 and this complex activates MG and reduce phagocytic capacity of MG against Aß-plaques
how/why can pharmacological targeting of specific inflammasomes improve cognitive function in AD (more than 1 answer is correct)?
a. NLRP3 inflammasome activation leads to upregulation of pro-inflammatory cytokines that is associated with MG activation
b. there is growing evidence that inhibition of NLRP3 PW promotes Aß clearance and stops MG-activation
c. NLRP3 inflammasome activation leads to upregulation of anti-inflammatory cytokines that improve microglial function and Aß clearance
d. NLRD1 agonists promote glutamate release from astrocytes and improve cognitive function thereby
a and b:
a. NLRP3 inflammasome activation leads to upregulation of pro-inflammatory cytokines that is associated with MG activation
b. there is growing evidence that inhibition of NLRP3 PW promotes Aß clearance and stops MG-activation
