L8- Neurodegenerative Disease, AD

Question 1

_____ is the most common cause of dementia among older adults

Answer 1

Alzheimer’s disease

Question 2

describe the clinical manifestation of Alzheimer’s

Answer 2

• slow onset of impaired higher intellectual function, memory impairment, impaired cognition
• altered mood, behavior
• late stages: severe dysfunction (aphasia, disorientation), but motor/sensory system intact

Question 3

(1) is used to confirm diagnosis of AD, and (2) is used to for initial diagnosis

Answer 3

1- autopsy

2- mental status exam (MSE)

Question 4

_____ is the predominant cause of death in AD

Answer 4

intercurrent pneumonia or other infections

Question 5

AD involves the accumulation of (1) and (2) which leads to (3)

Answer 5

1- Aβ amyloid protein (plaque)
2- tau protein (tangle)
3- neuronal death, inflammatory reaction

Question 6

Aβ protein is a product of (1) breakdown. When (1) is cleaved by (2) no Aβ results, but if cleaved by (3) then Aβ can form. (4) is the resulting progression after cleavage of (1) forms Aβ.

Answer 6

1- APP: amyloid precuror protein (transmembrane)
2- α-secretase, γ-secretase
3- β-secretase, γ-secretase
4- Aβ monomer –> polymer –> aggregated extracellularly => plaque formation + neuronal damage

Question 7

APP gene is found on chr.(1). Mutation of APP or (2) may facilitate (early/late) onset AD. In addition, (4) genetic condition also increases the risk of developing AD.

Answer 7

1- chr.21
2- γ-secretase (presenillin-1, 2)
3- early (familial AD)
4- trisomy 21, down syndrome

Question 8

Tau protein:

• (1) normal function, roughly
• Aβ will activate (2) in order to induce (3) change in tau
• tau in (3) form will then progress to (4) to induce (5)

Answer 8

1- microtubule associated protein, present in axons
2- kinases
3- hyperphosphorylate Tau –> cannot bind MTs
4- aggregate into neurofibrillary tangles (intracellularly)
5- neuronal death (exact mechanism is unknown) and extracellular aggregation

Question 9

AD is has mostly a (hereditary/sporadic) cause, include distribution. Among the familial causes early onset AD involves (2) and late onset AD involves (3).

Answer 9

1- sporadic, 80% — 20% hereditary

2- APP (chr,21) / Aβ, γ-secretase / Presenilin 1/2 (chr. 1, 14)

3- Tau protein, ApoE (chr. 19- E4 allele)

Question 10

Aβ may form from mutations in….

Answer 10

• APP (chr.21)
• trisomy 21
• γ-secretase: presenilin 1/2 (chr, 1, 14)

Question 11

gross appearance of AD

Answer 11

• atrophy of frontal, temporal, parietal lobes
• widening of sulci
• may lead to ex vacuo hydrocephalus (compensatory ventricular enlargement)

Question 12

list the main histological features of AD

Answer 12

• neuronal loss in cerebral cortex
• gliosis: astrocyte proliferation and hypertrophy
• neurofibrillary tangles (intracellular)
• neurotic plaques (extracellular)

Question 13

FTLD = (1):
-predominately due to (2) change, also seen in (3) neurodegenerative disease, or (4) change also seen in (5) neurodegenerative disease

Answer 13

1- frontotemporal lobar degeneration

2- Tau protein accumulation (FTLD-tau)
3- AD (but a younger age)

4- TDP43 aggregates, a DNA/RNA binding protein (FTLD-TDP)
5- ALS

Question 14

FTLD:

• (1) affected areas
• (2) clinical presentation
• (3) gross appearance

Answer 14

(frontotemporal lobar degeneration)
1- frontal and or temporal lobes

2- progressive behavioral changes or language problems (depends on affected lobe) –> memory disturbance develops later (unlike in AD)

3- atrophy of frontal and temporal lobes

Question 15

(1) is a type of FTLD where Tau accumulates in (2) fashion to form (3) microscopically

Answer 15

(frontotemporal lobar degeneration)
1- Pick’s disease
2- smooth round inclusions (neurofibrillary tangles)
3- Pick bodies