Lecture 17 4/2/24

Question 1

What are the general characteristics of misfolded proteins?

Answer 1

-normal amino acid sequence
-resistant to normal degradation; proteolysis cleavage sites become inaccessible
-form aggregates
-can act as template to alter normal proteins

Question 2

What is amyloid?

Answer 2

pathologic misfolded beta-pleated sheet protein

Question 3

How does amyloid appear grossly?

Answer 3

waxy tan enlargement of tissues and organs

Question 4

How does amyloid appear microscopically?

Answer 4

pale eosinophilic smooth to smudgy extracellular material

Question 5

What is the pathogenesis of AA amyloidosis?

Answer 5

-chronic inflammation anywhere in body
-interleukin-6 production
-acute phase protein serum amyloid A produced by hepatocytes
-defect in processing and clearance of SAA
-deposition of AA amyloid in tissues throughout body
-compression and obstruction resulting in organ dysfunction

Question 6

Where is AA amyloid commonly deposited?

Answer 6

-glomeruli
-liver
-intestinal lamina propria

Question 7

What are the characteristics of AA amyloidosis in waterfowl?

Answer 7

-liver is most commonly affected
-pododermatitis is often the predisposing inflammatory lesion

Question 8

What are the characteristics of AA amyloidosis in shar pei dogs?

Answer 8

-defect in expression of hyaluronic acid synthase 2 gene; causes wrinkles
-fragmented hyaluronic acid causes chronic inflammation
-average survival of 5 days after diagnosis

Question 9

Which cat breeds are predisposed to AA amyloidosis?

Answer 9

-Abyssinian (renal)
-siamese/oriental shorthair (liver/thyroid)

Question 10

Which tissue is most commonly affected by AA amyloidosis in older dogs and cattle?

Answer 10

glomeruli; leads to protein-losing nephropathy

Question 11

What is the only option for treating AA amyloidosis?

Answer 11

supportive care

Question 12

What are the characteristics of AL amyloidosis?

Answer 12

-associated with monoclonal production of Ig light chains/aggregates of light chains
-associated with focal or disseminated tumors of plasma cells
-not associated with inflammation

Question 13

What are the common sites of inflammation that cause hepatic AA amyloidosis in macaques?

Answer 13

-intestines
-joints

Question 14

What are the characteristics of pancreatic islet amyloidosis?

Answer 14

-most common in cats
-seen in cats with and without diabetes mellitus
-islet amyloid polypeptide (IAPP) co-secreted with insulin from beta cells

Question 15

What are the precursor proteins for each type of amyloidosis?

Answer 15

AA: serum amyloid A
AL: immunoglobulin light chains
Islet: islet amyloid polypeptide

Question 16

What are prion proteins?

Answer 16

naturally transmissible misfolded proteins with neurotoxic properties

Question 17

What is the pathogenesis of prions?

Answer 17

-ingested abnormally folded protein
-travels to brain and recruits normal proteins to misfold
-misfolded proteins aggregate and cause neuronal damage

Question 18

What is spongiform?

Answer 18

characterized by vacuoles or holes

Question 19

What are examples of prions?

Answer 19

-scrapie (sheep, goat)
-bovine spongiform encephalopathy
-transmissible mink encephalopathy
-feline spongiform encephalopathy
-chronic wasting disease (deer, elk)