6.11 Neurodegenerative Disease

Question 1

• 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

Answer 1

alzheimer disease

Question 2

neuropathology of AD:

• atrophy especially prominent in the _________, _______, and ________
• ______ lobe relatively preserved

Answer 2

temporal, amygdala, hippocampus

occipital

Question 3

alzheimer’s disease shows compensatory _________ due to diffuse atrophy

Answer 3

hydrocephalus

Question 4

2 primary protein aggregates in alzheimer disease?

Answer 4

beta amyloid plaques (from APP processing) and phosphorylated tau tangles

Question 5

APP gene on chromosome ______, shows AD pathology and cognitive disease by 40y

Answer 5

21 (Down syndrome)

Question 6

APP sequential cleavage by ___________ results in b-amyloid fibrils

Answer 6

beta/gamma secretase

Question 7

in AD tau is _________ and loses ability to bind microtubules

Answer 7

phosphorylated

Question 8

_______ are an AD hallmark and correlate better with dementia than amyloid

Answer 8

tau tangles

Question 9

• encodes for a cholesterol transporte
• increases deposition of fibrillar beta-amyloid
• strongest risk gene for late onset AD

Answer 9

apoE4

Question 10

centrall acting reversible acetylcholinesterase inhibitor, for AD treatment

Answer 10

donepezil

Question 11

NMDA receptor antagonist, blocks activity of the neurotransmitter glutamate

Answer 11

memantine

Question 12

• progressive dementia with fluctuations in cognition and arousal
• REM sleep behavior disorder
• visual hallucinations
• mild parkonsinism

Answer 12

Dementia with Lewy bodies

Question 13

hallmark of DLB is Lewy bodies, which are aggregates composed of?

Answer 13

alpha-synuclein, a synaptic protein

Question 14

• movement disorder: resting tremor, bradykinesia, and rigidity that progresses to involve both sides
• good early response to dopamine therapy

Answer 14

parkinson disease

Question 15

hallmark of Parkinson disease is _________ cell loss, lewy bodies, and loss of ______ dopamine content

Answer 15

substantia nigra compacta

striatal dopamine content

Question 16

mutations in __________ and ______ have been implicated in PD pathogenesis

Answer 16

LRRK2 (leucine rich repeat kinase 2) and alpha-synuclein

Question 17

MPTP and fertilizers/pesticides associated with?

Answer 17

Parkinson disease

Question 18

• progressive language deterioration, personality changes
• atrophy of frontal and temporal lobes
• many contain tau deposits

Answer 18

frontotemporal lobar degernation (FTLD)

Question 19

• onset after 40y, average course 5 years
• innapropriate social behavior, lack of empathy, loss of insight, repetitive or compulsive behavior, decreased motivation

Answer 19

Pick Disease (FTLD-tau)

Question 20

• lobar atrophy of frontal/temoral lobes
• preservation of parietal, occipital lobes
• church steeple, knife edge atrophy

Answer 20

Pick Disease (FTLD-tau)

Question 21

pick disease histopathology shows neuronal loss in ________, neurons containing _____ bodies with tau aggregates, and ______ cells are swollen pale neurons

Answer 21

outer cortical layers
pick
pick

Question 22

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

Answer 22

ALS

Question 23

most common genetic cause of ALS?

Answer 23

C9orf72 intronic hexanucleotide expansion

Question 24

ALS neuropathology shows _______ protein aggregates in motor neurons, which normally works to ensure long term survivial of motor neurons

Answer 24

TDP-43

Question 25

ALS shows muscle _________ in skeletal muscle, as well as fiber type grouping and denervation atrophy

Answer 25

fasiculations

Question 26

ALS drug that reduces glutamate

Answer 26

riluzole

Question 27

antioxidant, slows progression of ALS

Answer 27

edaravone