B7-051 Neurodegenerative Disease

Question 1

what is the pathologic protein in Alzheimer’s disease? [2]

Answer 1

Amyloid-beta
Tau

Question 2

what is the pathologic protein in huntington’s disease?

Answer 2

mutant huntingtin

Question 3

what is the pathologic protein in ALS? [3]

Answer 3

mutant superoxide dismutase
RNA-binding protein FUS
TDP-43

Question 4

what is the pathologic protein in frontotemporal lobar degeneration? [3]

Answer 4

RNA-binding protein FUS
Tau
TDP-43

depends on type

Question 5

what is the pathologic protein in chronic traumatic encephalopathy?

Answer 5

Tau

Question 6

what is the pathologic protein in limbic predominant age related encephalopathy?

Answer 6

TDP-43

Question 7

what is the pathologic protein in CJD?

Answer 7

PRP

Question 8

what is the pathologic protein in dementia with lewy bodies?

Answer 8

a-synuclein

Question 9

what is the pathologic protein in multiple system atrophy?

Answer 9

a-synuclein

Question 10

what is the pathologic protein in parkinson disease?

Answer 10

a-synuclein

Question 11

where does a-synuclein accumulate?

Answer 11

cytoplasm

Question 12

where does Amyloid-beta accumulate?

Answer 12

extracellular

Question 13

where does mutant huntingtin accumulate?

Answer 13

nucleus

Question 14

where does mutant superoxide dismutase 1 accumulate?

Answer 14

cytoplasm

Question 15

where does RNA-FUS protein accumulate?

Answer 15

cytoplasm

Question 16

where does tau accumulate?

Answer 16

cytoplasm

Question 17

where does TDP-43 accumulate?

Answer 17

cytoplasm

Question 18

where does PrP accumulate?

Answer 18

extracellular

Question 19

HHT gene is associated with what pathogenic protein?

Answer 19

mutant huntingtin

Question 20

SOD1 gene is associated with what pathogenic protein?

Answer 20

mutant superoxide dismutase 1

Question 21

FUS gene is associated with what pathogenic protein?

Answer 21

RNA binding protein FUS

Question 22

MAPT gene is associated with what pathogenic protein?

Answer 22

Tau

Question 23

LRRK2, PARK2, PARK7, PINK1, and SNCA genes are associated with what pathogenic protein?

Answer 23

a-synuclein

Question 24

APP, PSEN1, PSEN2 genes are associated with what pathogenic protein?

Answer 24

amyloid-beta

Question 25

C9orf72, GRN, TARDBP genes are associated with what pathogenic protein?

Answer 25

TDP-43

Question 26

Codon 129MM or VV, PRNP genes are associated with what pathogenic protein?

Answer 26

PrP

Question 27

inability to perceive more than a single object at a time

Answer 27

simultanagnosia

Question 28

simultanagnosia testing [2]

Answer 28

Navon figures overlapping objects

Question 29

[...] issues is often the first symptom in posterior cortical atrophy

Answer 29

reading (struggle to maintain place in text)

Question 30

posterior cortical atrophy is associated with [...] proteins

Answer 30

Alzheimer's (more of a visual variant, but still AD)

Question 31

posterior cortical atrophy is seen more often in [males/female] and has an [earlier/later] onset than typical AD

Answer 31

females earlier (50-60 yo)

Question 32

how is FDG-PET scan helpful in the diagnosis of neurodegenerative disease?

Answer 32

looks at the metabolism of glucose different NDDs cause failure in different brain networks corresponding to clinical phenotype

Question 33

85% of all NDDs are considered [...]

Answer 33

sporadic

Question 34

APP is on chromosome [...]

Answer 34

21 (why Down's syndrome patients have a predisposed risk to AD)

Question 35

autosomal dominant genes for AD [3]

Answer 35

APP PSEN1 PSEN2 (only represent about 1% of AD cases)

Question 36

risk factor gene for AD

Answer 36

APOE4

Question 37

1 copy of APOE4 increases the risk of AD by

Answer 37

3x

Question 38

2 copies of APOE4 increases the risk of AD by

Answer 38

11-15x

Question 39

largest modifiable risk factor for NDD

Answer 39

hearing loss

Question 40

disruption of [...] sleep increases the risk of NDD

Answer 40

slow wave (lymphatic flow clears proteins during slow wave sleep, **sleep apnea** and aging disrupt slow wave sleep)

Question 41

[...] network is the first network that changes in preclinical AD

Answer 41

default mode (APOE4 carriers show earlier deposition of this network)

Question 42

[amyloid/tau] correlates better with clinical phenotype

Answer 42

tau

Question 43

criteria for Lewy Body dementia [4]

Answer 43

REM sleep behavior disorder cognitive fluctuations hallucinations parkinsonism (must have 2 of 4)

Question 44

4 features defining Parkinsonism

Answer 44

rest tremor slow movements imbalance stiffness/rigidity (2 of 4)

Question 45

common themes across NDDs [4]

Answer 45

decreased slow wave sleep brain network dysfunction mitochondrial failure protein misfolding

Question 46

[...] and [...] likely play a role in protein balance stabilization and recycling of misfolded protein

Answer 46

aging mitochondrial failure

Question 47

decreased slow wave sleep causes decreased

Answer 47

clearance of cellular protein debris

Question 48

personality and behavior are most likely to be involved on the [...] hemisphere

Answer 48

right | non-dominant

Question 49

what lobes of the brain are affected in FTLD?

Answer 49

right frontal right anterior temporal (left lobe involvement would be much more likely to cause an aphasia variant)

Question 50

most NDDs show what pattern of clinical symptom changes?

Answer 50

insidious and progressive

Question 51

REM sleep behavior disorder is a strong predictor of [...] pathology

Answer 51

a-synuclein

Question 52

agraphia, acalculia, finger agnosia, and left-right disorientation indicate a lesion in the [...]

Answer 52

dominant parietal cortex (Gerstmann syndrome)

Question 53

agnosia of the contralateral side of the world indicates a lesion in the [...]

Answer 53

non-dominant parietal cortex (hemispatial neglect syndrome)

Question 54

FDG-PET is good for diagnosing

Answer 54

Lewy Body dementia

Question 55

DaT scan is good for diagnosing

Answer 55

Parkinson's (measures synaptic binding)

Question 56

loss of dopaminergic neurons in the substantia nigra

Answer 56

Parkinson disease

Question 57

symptoms of Parkinson's

Answer 57

Tremor Rigidity Akinesia Postural instability TRAP

Question 58

loss of GABAergic neurons in the striatum

Answer 58

Huntington disease

Question 59

how is Huntington disease inherited?

Answer 59

autosomal dominant- trinucleotide repeat

Question 60

HTT gene is on chromosome [...]

Answer 60

4

Question 61

symptoms of Huntington disease manifest between ages

Answer 61

30-50

Question 62

chorea athetosis agitation depression dementia symptoms of

Answer 62

Huntington disease

Question 63

atrophy of caudate and putamen with ex vacuo ventriculomegaly

Answer 63

Huntington disease

Question 64

neuronal death via NMDA receptor binding and glutamate excitotoxicity

Answer 64

Huntington disease

Question 65

early changes in personality or behavior or aphasia

Answer 65

frontotemporal dementia can have behavioral variant or aphasia variant depending on if dominant or non-dominant lobe is affected

Question 66

visual hallucinations dementia with fluctuating cognition REM sleep disorders

Answer 66

Lewy body dementia

Question 67

it is called Lewy Body dementia if cognitive and motor symptoms onset [...] apart

Answer 67

less than one year (if greater than one year, considered dementia secondary to Parkinsons)

Question 68

step-wise decline in cognitive ability with late onset memory impairment

Answer 68

vascular dementia

Question 69

MRI or CT shows multiple cortical/subcortical infarcts

Answer 69

vascular dementia

Question 70

2nd most common form of dementia in adults

Answer 70

vascular dementia

Question 71

rapidly progressive dementia with startle myoclonus

Answer 71

CJD