B7-051 Neurodegenerative Disease Flashcards
what is the pathologic protein in Alzheimer’s disease? [2]
Amyloid-beta
Tau
what is the pathologic protein in huntington’s disease?
mutant huntingtin
what is the pathologic protein in ALS? [3]
mutant superoxide dismutase
RNA-binding protein FUS
TDP-43
what is the pathologic protein in frontotemporal lobar degeneration? [3]
RNA-binding protein FUS
Tau
TDP-43
depends on type
what is the pathologic protein in chronic traumatic encephalopathy?
Tau
what is the pathologic protein in limbic predominant age related encephalopathy?
TDP-43
what is the pathologic protein in CJD?
PRP
what is the pathologic protein in dementia with lewy bodies?
a-synuclein
what is the pathologic protein in multiple system atrophy?
a-synuclein
what is the pathologic protein in parkinson disease?
a-synuclein
where does a-synuclein accumulate?
cytoplasm
where does Amyloid-beta accumulate?
extracellular
where does mutant huntingtin accumulate?
nucleus
where does mutant superoxide dismutase 1 accumulate?
cytoplasm
where does RNA-FUS protein accumulate?
cytoplasm
where does tau accumulate?
cytoplasm
where does TDP-43 accumulate?
cytoplasm
where does PrP accumulate?
extracellular
HHT gene is associated with what pathogenic protein?
mutant huntingtin
SOD1 gene is associated with what pathogenic protein?
mutant superoxide dismutase 1
FUS gene is associated with what pathogenic protein?
RNA binding protein FUS
MAPT gene is associated with what pathogenic protein?
Tau
LRRK2, PARK2, PARK7, PINK1, and SNCA genes are associated with what pathogenic protein?
a-synuclein
APP, PSEN1, PSEN2 genes are associated with what pathogenic protein?
amyloid-beta
C9orf72, GRN, TARDBP genes are associated with what pathogenic protein?
TDP-43
Codon 129MM or VV, PRNP genes are associated with what pathogenic protein?
PrP
inability to perceive more than a single object at a time
simultanagnosia
simultanagnosia testing [2]
Navon figures
overlapping objects
[…] issues is often the first symptom in posterior cortical atrophy
reading
(struggle to maintain place in text)
posterior cortical atrophy is associated with […] proteins
Alzheimer’s
(more of a visual variant, but still AD)
posterior cortical atrophy is seen more often in [males/female] and has an [earlier/later] onset than typical AD
females
earlier (50-60 yo)
how is FDG-PET scan helpful in the diagnosis of neurodegenerative disease?
looks at the metabolism of glucose
different NDDs cause failure in different brain networks corresponding to clinical phenotype
85% of all NDDs are considered […]
sporadic
APP is on chromosome […]
21
(why Down’s syndrome patients have a predisposed risk to AD)
autosomal dominant genes for AD [3]
APP
PSEN1
PSEN2
(only represent about 1% of AD cases)
risk factor gene for AD
APOE4
1 copy of APOE4 increases the risk of AD by
3x
2 copies of APOE4 increases the risk of AD by
11-15x
largest modifiable risk factor for NDD
hearing loss
disruption of […] sleep increases the risk of NDD
slow wave
(lymphatic flow clears proteins during slow wave sleep, sleep apnea and aging disrupt slow wave sleep)
[…] network is the first network that changes in preclinical AD
default mode
(APOE4 carriers show earlier deposition of this network)
[amyloid/tau] correlates better with clinical phenotype
tau
criteria for Lewy Body dementia [4]
REM sleep behavior disorder
cognitive fluctuations
hallucinations
parkinsonism
(must have 2 of 4)
4 features defining Parkinsonism
rest tremor
slow movements
imbalance
stiffness/rigidity
(2 of 4)
common themes across NDDs [4]
decreased slow wave sleep
brain network dysfunction
mitochondrial failure
protein misfolding
[…] and […] likely play a role in protein balance stabilization and recycling of misfolded protein
aging
mitochondrial failure
decreased slow wave sleep causes decreased
clearance of cellular protein debris
personality and behavior are most likely to be involved on the […] hemisphere
right
non-dominant
what lobes of the brain are affected in FTLD?
right frontal
right anterior temporal
(left lobe involvement would be much more likely to cause an aphasia variant)
most NDDs show what pattern of clinical symptom changes?
insidious and progressive
REM sleep behavior disorder is a strong predictor of […] pathology
a-synuclein
agraphia, acalculia, finger agnosia, and left-right disorientation indicate a lesion in the […]
dominant parietal cortex
(Gerstmann syndrome)
agnosia of the contralateral side of the world indicates a lesion in the […]
non-dominant parietal cortex
(hemispatial neglect syndrome)
FDG-PET is good for diagnosing
Lewy Body dementia
DaT scan is good for diagnosing
Parkinson’s
(measures synaptic binding)
loss of dopaminergic neurons in the substantia nigra
Parkinson disease
symptoms of Parkinson’s
Tremor
Rigidity
Akinesia
Postural instability
TRAP
loss of GABAergic neurons in the striatum
Huntington disease
how is Huntington disease inherited?
autosomal dominant- trinucleotide repeat
HTT gene is on chromosome […]
4
symptoms of Huntington disease manifest between ages
30-50
chorea
athetosis
agitation
depression
dementia
symptoms of
Huntington disease
atrophy of caudate and putamen with ex vacuo ventriculomegaly
Huntington disease
neuronal death via NMDA receptor binding and glutamate excitotoxicity
Huntington disease
early changes in personality or behavior
or aphasia
frontotemporal dementia
can have behavioral variant or aphasia variant depending on if dominant or non-dominant lobe is affected
visual hallucinations
dementia with fluctuating cognition
REM sleep disorders
Lewy body dementia
it is called Lewy Body dementia if cognitive and motor symptoms onset […] apart
less than one year
(if greater than one year, considered dementia secondary to Parkinsons)
step-wise decline in cognitive ability with late onset memory impairment
vascular dementia
MRI or CT shows multiple cortical/subcortical infarcts
vascular dementia
2nd most common form of dementia in adults
vascular dementia
rapidly progressive dementia with startle myoclonus
CJD
