Week 6.5

Question 1

What is the protein aggregate found in AD, PD, HD, CJD, and ALS?

Answer 1

• AD: beta-amyloid, tau tangles
• PD: alpha-synuclein
• HD: huntingtin
• CJD: prion
• ALS: TDP-43

Question 2

Alzheimer’s has a typical onset of what age?

Answer 2

sixty years old

Question 3

Describe the gross pathology of Alzheimer’s disease.

Answer 3

• early medial temporal atrophy
• occipital lobe relatively spared
• large ventricles and hydrocephalus ex vacuo

Question 4

Alzheimer’s typically spares what lobe of the brain?

Answer 4

occipital

Question 5

What vascular disease is associated with Alzheimer’s disease?

Answer 5

cerebral beta-amyloid angiopathy

Question 6

What are Hirano bodies?

Answer 6

actin aggregates common in the hippocampal neurons of those with Alzheimer’s

Question 7

Beta-amyloid is a product of what metabolic process?

Answer 7

cleavage of the APP protein by beta- and gamma-secretase

Question 8

The APP gene is located on which chromosome?

Answer 8

21

Question 9

Down’s syndrome patients often suffer from early onset of what dementia?

Answer 9

Alzheimer’s

Question 10

A functional tau protein plays what physiologic role?

Answer 10

it stabilizes microtubules

Question 11

Which protein aggregate is more strongly associated with the onset of symptoms in Alzheimer’s?

Answer 11

the appearance of tau tangles

Question 12

Tau tangles preferentially affect which brain regions?

Answer 12

• amygdala
• hippocampus
• lateral geniculate nucleus

Question 13

What causes tau to become pathological?

Answer 13

it is phosphorylated

Question 14

What are some genetic risk factors for Alzheimer’s disease?

Answer 14

presenilin-1 and ApoE4

Question 15

The ApoE gene encodes a protein that does what?

Answer 15

it is a cholesterol transporter apolipoprotein

Question 16

What is donepezil?

Answer 16

a centrally acting reversible AChE inhibitor that works to treat those with Alzheimer’s disease

Question 17

Which NT system is affected in those with Alzheimer’s?

Answer 17

reduced acetylcholine

Question 18

Name two drugs commonly used to treat Alzheimer’s.

Answer 18

• donepezil (AChE inhibitor)

- memantine (NMDA antagonist)

Question 19

Lewy Bodies are a feature of what two disease?

Answer 19

Parkinson’s and dementia with Lewy Bodies

Question 20

What are the symptoms of Dementia with Lewy Bodies?

Answer 20

• progressive dementia with fluctuations
• REM sleep disorder
• visual hallucinations
• variable parkinsonism

Question 21

Lewy bodies are comprised of what protein?

Answer 21

alpha-synuclein

Question 22

What genetic risk factor exists for dementia with levy bodies?

Answer 22

ApoE4

Question 23

Autosomal dominant parkinson’s diseases is the result of a mutation in which gene?

Answer 23

leucine rich repeat kinase 2

Question 24

Sporadic parkinson’s has been linked to mutations in which gene?

Answer 24

glucocerebrosidase

Question 25

Frontotemporal lobar dementias share what features?

Answer 25

- progressive language deterioration - personality changes - atrophy of temporal and frontal lobes with sparing of parietal and occipital

Question 26

Pick's diseases is characterized by what protein aggregate?

Answer 26

tauopathy

Question 27

Pick's disease has an onset of when?

Answer 27

20-60 years of age

Question 28

What are the symptoms of Pick's disease?

Answer 28

- personality change - loss of motivation - lack of empathy - inappropriate behavior - language disturbance - lack of insight

Question 29

What is the most common genetic cause of ALS?

Answer 29

C9orf72

Question 30

What protein aggregate is the hallmark of ALS?

Answer 30

TDP-43

Question 31

What is the normal function of TDP-43?

Answer 31

work with FUS to ensure the long-term survival of motor neurons

Question 32

What white mater tract is most affected by ALS?

Answer 32

anterior and lateral corticospinal tracts