Alzheimeres Disease

Question 1

What are the characteristics microscopic findings in AD?

Answer 1

Neuritic plaques and neurofibrillary tangles

Question 2

Describe the structure of neuritic plaques?

Answer 2

Amyloid core consisting Ab protein surrounded by a halo of dystrophic, tau immunoreactive neuritis and activated microglia.

Question 3

How are Ab amyloid produced?

Answer 3

From a precursor protein called APP (amyloid precursor protein). This is cleaved by alpha, Beta and gamma secretases. The B secretase product is further cleaved by Gamma secretes that lead to Ab42 amyloid production.

Question 4

What are neurofibriallary tangles?

Answer 4

They are silver staining neuronal cytoplasmic fibrils that are abnormally phosphrylated tau protein.

They are paired helical filaments in EM

Question 5

What is the function of tau proteins?

Answer 5

Tau binds and stabilises microtubules that help with neurotransmission, axonal transport. Once hyperphoshorylted these functions are disrupted.

Question 6

what are the four main chromosomes involved in the pathogenesis of AD?

Answer 6

1, 14, 19 and 21

Question 7

Which chromosome has the APP gene?

Answer 7

21

Question 8

What is the most the most common genetic abnormality in patients with early onset AD?

Answer 8

Presenilin 1 on ch 14. PS 1 encodes S182.

Patienst have elevated levels of Ab42, and Ps-1 is involved in the clevage of APP at the gamma secretase site.

Question 9

Which ch is Ps-2 gene?

Answer 9

ch 1

Question 10

What ch is Apo e gene located in? What alleles are present?

Answer 10

Ch 19, 3 alleles 2,3 and 4

Question 11

wht is the risk of AD with one allele of apoe gene vs homozygtic apo e alleles?