L44 Patho and Pharm of AD Flashcards
T or F: There is a 2:1 ratio female:male for AD
True
5 sxs of AD
- memory loss
- impaired ability to learn, reason
- impaired ability to carry out daily activites, confusion, untidiness
- anxiety, suspicion, hallucination
- motor dysfxn in late-stages
AD neuropathology: Loss of ______
brain volume, essentially brain shrinking
amyloid plaques (2 things)
extracellular
consist of amyloid-B peptide (AB)
neurofibrillary tangles (2 things)
intracellular
consist of hyper-phosphorylated tau
T or F: AD neuropathology primarily affects areas of high cognitive fxn
tru
Memory formation/consolidation:
a. entorhinal cortex
b. hippocampus
c. basal forebrain cholinergic systems
d. neocortex
a. entorhinal cortex
b. hippocampus
Learning (just learning):
a. entorhinal cortex
b. hippocampus
c. basal forebrain cholinergic systems
d. neocortex
c. basal forebrain cholinergic systems
Memory, learning, cognition:
a. entorhinal cortex
b. hippocampus
c. basal forebrain cholinergic systems
d. neocortex
d. neocortex
synapse loss leads to reduced levels of which neurotransmitters
ACh (mostly)
serotonin
norepinephrine
dopamine
what chromosome is the APP gene located on?
Chromosome 21
What is the AB peptide released from and by the activity of what two things
transmembrane amyloid precursor protein (APP), B-secretase (BACE1) and y-secretase
Mutations in the APP gene favor cleavage by what or what
B or y secretase
what does cleavage of APP by b or y-secretase result in?
production of more AB42 relative to AB40- **
what are two components of the y-secretase
Presenilin 1 and presenilin 2
what do PSEN1 and PSEN2 do
alter APP cleavage by y-secretase resulting in production of more AB42 compared to AB40
What does excessive phosphorylation of tau lead to?
neurofibrillary tangles
what leads to excessive phosphorylation of tau
release of cytokines from kinase activation after binding of Ab
what do neurofibrillary tangles do?
lead to the disruption of cytoskeleton and disrupts axonal trafficking
what is tau’s normal function?
to stabilize microtubules
what effect does AP aggregation have on microglia
triggers microglial activation to clear amyloid from the brain
over-activated microglia is a feature of what
neurological diseases
what do activated microglia release? What does this cause?
pro-inflammatory cytokines (prostaglandins, interleukins, tumor necrosis factor-a). causes neuroinflammation (no shit)
activated microglia also release what and what? what does this cause
reactive nitrogen and oxygen species, causes oxidative stress (no shit again)
Individuals with one or two of the following alleles have an increased risk of AD?
A. ApoE4
B. ApoE2
A. ApoE4
Inheritance of which of the following alleles decreases AD risk?
A. ApoE4
B. ApoE2
B. ApoE2
which of the following is protective?
A. ApoE4
B. ApoE2
B. ApoE2
Which of the following statements is TRUE?
A. Aβ accumulation results in an inhibition of kinases that phosphorylate tau.
B. Interleukins contribute to synaptic loss in AD.
C. The presence of one or two ApoE2 alleles increases the risk of AD.
D. Synaptic degeneration in AD triggers a loss of acetylcholine but not dopamine.
B. Interleukins contribute to synaptic loss in AD.
3 cholinesterase inhibitors
donepezil (Aricept)
Rivastigmine
Galantamine
Specific, reversible inhibitor of acetylcholinesterase
A. donepezil (Aricept)
B. Rivastigmine
C. Galantamine
A. Donepezil (Aricept)
Inhibits acetylcholinesterase and butyrylcholinesterase
A. Donepezil (Aricept)
B. Rivastigmine
C. Galantamine
B. Rivastigmine
Selective, reversible inhibitor of acetylcholinesterase and enhances the action of ACh on nicotinic receptors (increases ACh release from cholinergic neurons)
A. Donepezil (Aricept)
B. Rivastigmine
C. Galantamine
C. Galantamine
T or F: cholinesterase inhibitors treat symptoms of AD
True
medication that falls under anti-glutamatergic therapy
memantine
NMDA antagonist that blocks glutamatergic neurotransmission via a noncompetitive mechanism, reduces excitotoxicity
A. Donepezil (Aricept)
B. Rivastigmine
C. Galantamine
D. Memantine
D. Memantine
what is the drug combo of Memantine ER + donepezil called?
Namzaric
Radiolabeled agent specific for tau
F-FlorTAUcipir
radiolabeled agent that binds B-amyloid, visualized by PET scanning
Florbetapir
T or F: Pet scans are an effective way of observing amyloid in parkinsons
nah this is false dog its AD
Impaired judgement or executive function is a more common initial sx than the memory loss characteristic of AD
A. Vascular Dementia
B. Dementia with Lewy Bodies
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
A. Vascular dementia
Occurs as a result of brain injury associated with vascular disease or stroke.
A. Vascular Dementia
B. Dementia with Lewy Bodies
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
A. Vascular Dementia (duh)
combination of cognitive decline and parkinsonian sxs.
A. Vascular Dementia
B. Dementia with Lewy Bodies
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
B. Dementia with Lewy Bodies
visual hallucinations are a core diagnostic feature.
A. Vascular Dementia
B. Dementia with Lewy Bodies
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
B. Dementia with Lewy Bodies
Disinhibited behavior, poor impulse control, antisocial behavior
A. Vascular Dementia
B. Dementia with Lewy Bodies
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
tau accumulations
A. Vascular Dementia
B. Dementia with Lewy Bodies
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
C. Frontotemporal Dementia (FTD) - e.g. pick’s disease
Which of the following statements is FALSE?
A. Donepezil is a more specific acetylcholinesterase inhibitor than rivastigmine.
B. Memantine interferes with Ca2+ accumulation in neurons exposed to glutamate.
C. Lewy bodies are a pathological hallmark of PD and DLB.
D. Small molecules that inhibit tau phosphatases are drug candidates for AD.
D. Small molecules that inhibit tau phosphatases are drug candidates for AD.
