6.11 Neurodegenerative Disease Flashcards
- most common cause of dementia
- progressive los of higher intellectual function: affects memory, language, judgement, mood, behavior
- usually sporadid, younger may be autosomal dominant
- definitive diagnosis made at autopsy
alzheimer disease
neuropathology of AD:
- atrophy especially prominent in the _________, _______, and ________
- ______ lobe relatively preserved
temporal, amygdala, hippocampus
occipital
alzheimer’s disease shows compensatory _________ due to diffuse atrophy
hydrocephalus
2 primary protein aggregates in alzheimer disease?
beta amyloid plaques (from APP processing) and phosphorylated tau tangles
APP gene on chromosome ______, shows AD pathology and cognitive disease by 40y
21 (Down syndrome)
APP sequential cleavage by ___________ results in b-amyloid fibrils
beta/gamma secretase
in AD tau is _________ and loses ability to bind microtubules
phosphorylated
_______ are an AD hallmark and correlate better with dementia than amyloid
tau tangles
- encodes for a cholesterol transporte
- increases deposition of fibrillar beta-amyloid
- strongest risk gene for late onset AD
apoE4
centrall acting reversible acetylcholinesterase inhibitor, for AD treatment
donepezil
NMDA receptor antagonist, blocks activity of the neurotransmitter glutamate
memantine
- progressive dementia with fluctuations in cognition and arousal
- REM sleep behavior disorder
- visual hallucinations
- mild parkonsinism
Dementia with Lewy bodies
hallmark of DLB is Lewy bodies, which are aggregates composed of?
alpha-synuclein, a synaptic protein
- movement disorder: resting tremor, bradykinesia, and rigidity that progresses to involve both sides
- good early response to dopamine therapy
parkinson disease
hallmark of Parkinson disease is _________ cell loss, lewy bodies, and loss of ______ dopamine content
substantia nigra compacta
striatal dopamine content
mutations in __________ and ______ have been implicated in PD pathogenesis
LRRK2 (leucine rich repeat kinase 2) and alpha-synuclein
MPTP and fertilizers/pesticides associated with?
Parkinson disease
- progressive language deterioration, personality changes
- atrophy of frontal and temporal lobes
- many contain tau deposits
frontotemporal lobar degernation (FTLD)
- onset after 40y, average course 5 years
- innapropriate social behavior, lack of empathy, loss of insight, repetitive or compulsive behavior, decreased motivation
Pick Disease (FTLD-tau)
- lobar atrophy of frontal/temoral lobes
- preservation of parietal, occipital lobes
- church steeple, knife edge atrophy
Pick Disease (FTLD-tau)
pick disease histopathology shows neuronal loss in ________, neurons containing _____ bodies with tau aggregates, and ______ cells are swollen pale neurons
outer cortical layers
pick
pick
lethal neurodegenerative disorder of motor neurons with subtle onset of focal weakness, usually in limbs or bulbar muscles progressing to paralysis of nearly all skeletal muscle with respiratory paralysis
ALS
most common genetic cause of ALS?
C9orf72 intronic hexanucleotide expansion
ALS neuropathology shows _______ protein aggregates in motor neurons, which normally works to ensure long term survivial of motor neurons
TDP-43
ALS shows muscle _________ in skeletal muscle, as well as fiber type grouping and denervation atrophy
fasiculations
ALS drug that reduces glutamate
riluzole
antioxidant, slows progression of ALS
edaravone
