Neurodegenerative disease Flashcards
What are 3 common features of neurodegenerative disease?
selective vulnerability of specific neurons & systems
misfolded and/or aggregated proteins
sporadic and familial forms
What misfolded protein is associated with alzheimers?
amyloid-B and tau
What misfolded protein is associated with parkinson’s?
a-synuclein
What misfolded protein is associated with frontotemporal lobar degeneration?
tau, ubiquitin, TDP-43
What protein is found in lewy bodies?
a-synuclein
What region is degenerated in parkinson’s?
extrapyramidal system
What region is degenerated in alzheimer’s?
cerebral cortex (higher order association cortices and limbic system)
What region is degenerated in Huntington’s?
extrapyramidal system
What region is degenerated in ALS?
pyramidal system
What neurodegenerative disease has AD inheritance?
huntington’s disease
How might environmental toxins induce neurodegeneration?
reduce mitochondrial funciton; decrease ATP production and increased oxidative stress
How might neuronal metabolism induce neurodegeneration?
is oxidative
How might aging induce neurodegeneration?
affects mitochondrial function
loss of protective enzymes and molecules
progressive hits
Which complex is particularly vulnerable to free radical injury?
complex 1
How does excessive glutamate cause excitoxicity?
persistent activation of NMDA receptors--> excess intracellular calcium--> ATP depletion--> cell death--> more excessive glutamate
What mechansims do cells have to deal with oxyradicals?
ascorbate glutathione superoxide dismutase catalase (these are depeleted with age)
What is the most common form of dementia?
Alzheimer’s disease
What symptoms define alzheimer’s clinically?
impairments in recent memory
decline in cognitive function
results in functional impairment socially or occupationally
WHat are the cognitive domans affected by alzheimers?
memory language abstract thinking & judgement visuospatial or perceptual skills prxis executive function
How do you make a definitive diagnosis of (Dementia of alzheimers type) DAT?
clinical criteria for probably DAT and hisopathologic evidence of DAT
What are the cirteria for probable DAT?
dementia two areas of cognitive impairment progression over time normal sensorium age of onset between 40-90yrs no other disease contributing to the dementia
What are the criteria for possible DAT?
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
What are the clinical findings in stage 1 DAT?
memory-new learning defective, remote recall mildly impaired
poor complex construction/visuospatial skills
poor word generation/anomia
psych features depression/delusions
What are the clinical findings in stage 2 DAT?
memory-recent and remote racall more severely impaired
visuospatial skills-poor constructin and spatial disorientation
acalculia
psych features-delusions
