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BMB Test 3 > B7.051 Neurodegenerative Disease > Flashcards

B7.051 Neurodegenerative Disease Flashcards

1
Q

definition of neurodegenerative disease

A

progressive decline in a neurologic function or functions, arising from neurodysfunction that eventually includes neuron loss/death

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2
Q

are neurodegenerative disorders primary disorders of neurons

A

not always

can be astrocytes or microglial cells

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3
Q

subjective cognitive impairment

A

patient believes they have cognitive impairment

not observable by physician

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4
Q

mild cognitive impairment

A

patient believes they have cognitive impairment
changes observable by physician
not enough impairment to interfere with daily life

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5
Q

dementia

A

cognitive decline that impacts ADLs and is recognizable by physician

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6
Q

different syndromes associated with neurodegenerative disorders

A 
cognitive/behavior
movement
strength
coordination
spasticity
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7
Q

anatomic locations of neurodegenerative disorder focus

A 
cortex
white matter
cerebellum
spinal cord
peripheral nerve
by system (motor, basal ganglia, vision, hearing, autonomic, transmitter)
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8
Q

histopathological classes of neurodegenerative diseases

A 
amyloidoses
tauopathies
synucleinopathies
TDP43-opathies
prion disorders
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9
Q

what is an amyloid

A

B sheet configured peptide

green birefringence on congo red staining

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10
Q

common synucleinopathies

A

Lewy body diseases

  • lewy body dementia
  • parkinson’s
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11
Q

secretases associated with APP

A

a, B, y secretase
all cut at different locations on APP
from top to bottom: B site, a site, y site

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12
Q

non-amyloidogenic processing of APP

A
  1. a secretase cleaves
    - soluble APPa
    - APP-CTF83 in membrane
  2. APP-CTF82 is cleaved within the membrane by y secretase
    - AICD (amyloid intracellular domain)
    - P3
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13
Q

amyloidogenic processing of APP

A
  1. B secretase cleaves
    - sAPPB
    - APP-CTF99
  2. APP-CTF99 is cleaved within the membrane by y secretase
    - AB : goes on to form plaques
    - AICD
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14
Q

characteristics of AB protein

A

can be in an a or B conformation, B sheet high probability
central hydrophobic cluster
highly hydrophobic region
fold in order to sequester the hydrophobic region from the aqueous environment

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15
Q

transformation of AB protein into plaque

A

oligomers (2-12 amyloid pieces)
fibrils of multiple oligomers
plaque of multiple fibrils

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16
Q

are AB plaques toxic?

A

unclear

  • could be toxic to the extracellular environment
  • AB proteins themselves could be transported into cell and be toxic to intracellular components
  • may not be toxic at all
17
Q

how does an AB oligomer become alternatively folded

A

random nucleation event

-thermodynamically unfavorable refolding

18
Q

what happens as a result of alternative folding

A

alternatively folded oligomers coerce other members of protein family to fold in the same manner (“seeding”)
standard oligomers drawn into alternatively folded conformation
fibril formation

19
Q

what happens with lengthening of an alternatively folded fibril

A

changes from soluble to insoluble

insoluble fibrils aggregate to form plaque

20
Q

diagnosis of neurodegenerative disease

A 
clinical syndrome
neuroimaging
CSF biomarkers
blood biomarkers
genotyping
21
Q

CSF biomarkers in alzheimer’s

A

b amyloid decreases
tau protein increases
AB/tau ratio examined

22
Q

relevant alzheimers genotyping

A

presenilin 1
presenilin 2
APP

23
Q

treatment approaches for neurodegenerative disease

A 
supportive
symptomatic
disease modifying
prevention
-primary
-secondary
24
Q

most common rate of neurodegenerative changes

A

insidious/chronic

25
Q

cognition/ behavior neurodegenerative diseases

A

Alzheimers
frontotemporal dementias
prior disorders
lewy body dementia

26
Q

movement neurodegenerative diseases

A 
parkinsons
lewy body dementia
progressive supranuclear palsy
corticobasal degeneration
MSA
huntingtons
27
Q

strength neurodegenerative diseases

A

ALS

28
Q

coordination neurodegenerative diseases

A

spinocerebellar ataxias

29
Q

spasticity neurodegenerative diseases

A

hereditary parapareses

30
Q

amyloid neurodegenerative diseases

A

alzheimers

31
Q

tau neurodegenerative diseases

A

frontotemporal dementias
progressive supranuclear palsy
corticobasal degeneration

32
Q

a synuclein neurodegenerative diseases

A

Parkinson’s
lewy body dementia
MSA

33
Q

TDP43 neurodegenerative diseases

A

ALS

frontotemporal dementias

BMB Test 3 (21 decks)

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