39: Neurodegenerative Disorders Flashcards
main characteristics of neurodegenerative disorders
- progressive and irreversible loss of neurons
- due to both genetic and environmental factors
- pathology including cellular aggregation of misfolded prtns
loss of hippoampal and cortical neurons results in impaired memory formation and cognitive deficits =
alzheimers disease
loss of dopaminergic neurons in basal ganglia leads to altered movement control
parkinson’s disease and huntington’s disease
degeneration of cortical and spinal motor neurons results in muscular weakness
amyotrophic lateral sclerosis ALS
what prtns accumulate in alzheimers?
b-amyloid plaques and neurofibrillary tangles
what prtns accumulate in ALS? parkinson’s disease?
intracytoplasmic aggregrates
parkinsons: alpha-synuclein
what prtns accumulate in huntington’s disease?
intranuclear inclusions of huntingin prtn
extracellular prion amyloid plaques located in different brain regions =
prion disease (transmissible spongiform encephalopathy TSE)
what are the cognitive symptoms of AD?
- loss of short term memory
- aphasia
- apraxia
- agnosia
- disorienation
what are the noncognitive symptoms of AD?
- depressioin
- psychotic symptoms
initial manifestation of a progressive degenerative dementia
mild cognitive impairment MCI
MCI can progress to AD ata rate of 10-15% per year
not yet dementia
language impairment, decreased comprehension, disorientation, and sleep disorders indicate what stage of AD
moderate (2-10 yrs)
dependence, delusion, agitation and incapacitation indicate what stage of alzheimers disease?
severe (8-12 yrs)
3 pathological signs of AD
- neuronal degeneration and cortical atrophy
- neuritic plaques (amyloid or senile)
- neurofibrillary tangles
these changes eventually lead to clinical symptoms, but they begin years before the onset of symptoms
5 brain areas typically affected by AD
hippocampus nucleus of meynert temporal lobe frontal lobe parietal lobe
cholinergic hypothesis
deficiency of Ach causes AD
amyloid hypothesis
extracellular accumulations of b-amyloid peptides that are toxic to neurons
but deposition of b-a plaques does not correlate well with neuronal loss
why do people with down syndrome experience AD at an early age?
APP gene is on chromosome 21, people with trisomy 21 (down syndrome) have extra copies of APP and commonly exhibit AD by age of 40
early onset AD is associated with ___ late onset AD is associated with _____
APP, PSEN1 and PSEN2
E4 allele of APOE (ApoE enhances proteolytic breakdown and clearance of a- within and between cells)
50% of all AD patients have this allele
ApoE-E4 isoform for ApoE
Tau hypothesis
hyperphosphorylation of Tau aggregates and forms neurofibrilary tangles
tau provides support to microtubules and neuronal cytoskelton
first line therapy for symptomatic treatment of cognitive impairments in mild to moderate AD
cholinesterase inhibitors
reduce the breakdown of endogenously released ACh resulting in greater activation of postsynaptic ACh receptors
MOA donepezil
inhibits Acetylcholinesterase
MOA rivastigmine
inhibits both acetylcholinesterase and butyrylcholinesterase
