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Neuro > Neurodegenerative disease > Flashcards

Neurodegenerative disease Flashcards

1
Q

What are 3 common features of neurodegenerative disease?

A

selective vulnerability of specific neurons & systems
misfolded and/or aggregated proteins
sporadic and familial forms

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2
Q

What misfolded protein is associated with alzheimers?

A

amyloid-B and tau

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3
Q

What misfolded protein is associated with parkinson’s?

A

a-synuclein

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4
Q

What misfolded protein is associated with frontotemporal lobar degeneration?

A

tau, ubiquitin, TDP-43

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5
Q

What protein is found in lewy bodies?

A

a-synuclein

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6
Q

What region is degenerated in parkinson’s?

A

extrapyramidal system

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7
Q

What region is degenerated in alzheimer’s?

A

cerebral cortex (higher order association cortices and limbic system)

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8
Q

What region is degenerated in Huntington’s?

A

extrapyramidal system

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9
Q

What region is degenerated in ALS?

A

pyramidal system

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10
Q

What neurodegenerative disease has AD inheritance?

A

huntington’s disease

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11
Q

How might environmental toxins induce neurodegeneration?

A

reduce mitochondrial funciton; decrease ATP production and increased oxidative stress

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12
Q

How might neuronal metabolism induce neurodegeneration?

A

is oxidative

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13
Q

How might aging induce neurodegeneration?

A

affects mitochondrial function
loss of protective enzymes and molecules
progressive hits

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14
Q

Which complex is particularly vulnerable to free radical injury?

A

complex 1

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15
Q

How does excessive glutamate cause excitoxicity?

A 
persistent activation of NMDA receptors-->
excess intracellular calcium-->
ATP depletion-->
cell death-->
more excessive glutamate
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16
Q

What mechansims do cells have to deal with oxyradicals?

A 
ascorbate
glutathione
superoxide dismutase
catalase 
(these are depeleted with age)
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17
Q

What is the most common form of dementia?

A

Alzheimer’s disease

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18
Q

What symptoms define alzheimer’s clinically?

A

impairments in recent memory
decline in cognitive function
results in functional impairment socially or occupationally

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19
Q

WHat are the cognitive domans affected by alzheimers?

A 
memory
language
abstract thinking & judgement
visuospatial or perceptual skills
prxis
executive function
20
Q

How do you make a definitive diagnosis of (Dementia of alzheimers type) DAT?

A

clinical criteria for probably DAT and hisopathologic evidence of DAT

21
Q

What are the cirteria for probable DAT?

A 
dementia
two areas of cognitive impairment
progression over time
normal sensorium 
age of onset between 40-90yrs
no other disease contributing to the dementia
22
Q

What are the criteria for possible DAT?

A

atypical onset/presentation/progression
No systemic or other brain disease capable of producing dementia
gradually progressive decline in a single intellectual function in the absence of any other identifiable cause

23
Q

What are the clinical findings in stage 1 DAT?

A

memory-new learning defective, remote recall mildly impaired
poor complex construction/visuospatial skills
poor word generation/anomia
psych features depression/delusions

24
Q

What are the clinical findings in stage 2 DAT?

A

memory-recent and remote racall more severely impaired
visuospatial skills-poor constructin and spatial disorientation
acalculia
psych features-delusions

25
Q

What are the clinical findings in stage 3 DAT?

A

intellectual functions severely impaired
urinary and fecal incontinence
limb rigidity and flexion posture

26
Q

What gross features are seen in DAT?

A

decreased brain weight
atrophy of gyri and widening of sulci
increased size of ventricles (hydrocephalus ex vacuo)

27
Q

What are diffuse plaques made of?

A

extracellular accumulation of Abeta protein

28
Q

What are neuritic plaques made of?

A

extracellular accumulation of Abeta protein and tau containing neurites

29
Q

Which type of alzheier’s disease senile plaques are more closely associated with cognitive decline?

A

neuritic plaque

30
Q

How commonly is cerebral amyloid angiopathy seen in AD?

A

almost always, but can occur in absence of AD

31
Q

What is a neurofibrillary tangle?

A

intraneuronal accumulation of an abnormally phosphorylated form of tau, a normal MT assoc protein

32
Q

What is the relationship between NFTs and AD?

A

unknown

33
Q

What is the biggest risk factor for AD?

A

age

34
Q

What are the key features of early onset AD?

A

onset <60-65yo

often autosomal dominant mutation, highly penetrant

35
Q

What are the key features of late onset AD?

A

onset >60-65

no mendelian pattern of inheritance

36
Q

What is amyloid precursor protein?

A

transmenbrane glycoprotein
prescursor to Abeta protein
gene on chromosome 21

37
Q

What age range to people with trisomy 21 develop AD in?

A

late 30s

38
Q

If alpha secretase cleaves within Abeta sequence, what happens?

A

normal, no Abeta produced

39
Q

If beta secretase cleaves within Abeta sequence what happens?

A

Abeta produced

40
Q

What genes are associated with early onset AD?

A

presenilin 1
APP
Presenilin 2

41
Q

What is the only established risk factor for late onset AD?

A

ApoE gene/apolipoprotien E

presence of E4 modifies genetic risk (leads to increased Abeta deposition)

42
Q

What types of dementia is cholinergic signaling deficiency present in?

A

AD
Dementia with lewy bodies
vascular dementia

43
Q

Which 3 cholinesterase inhibitors are currently in use for dementia?

A

donepezil
rivastigmine
galantamine

44
Q

What are some side effects of cholinesterase inhibitors?

A

GI problems
muscle cramping
abnormal dreams

45
Q

How does the drug memantine work?

A

is an NMDA channel blocker, has some efficacy in slowing AD disease prgression

46
Q

What are some side effects of memantine?

A

headache

dizziness

Neuro (14 decks)

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