Amyloidosis

Question 1

What is the structure of Amyloid proteins?

Answer 1

Non-branched Fibrils made of ß-sheet polypeptide chains.

Question 2

T or F: while the structure of the over-produced or misfolded protein is the different, the structure of the amyloid remains the same.

Answer 2

True, All amyloid is unbranched ß-sheet

Question 3

What are the 2 general categories of protein that make amyloid?

Answer 3

1. Normal Proteins that have inherent tendency to fold improperly and make fibrils and do this when in high amounts
2. MUTANT proteins that are prone to misfolding and aggregation

Question 4

What are the 2 types of amyloidosis?

• what is the cause of each of these?
• prototypical example?

Answer 4

Primary:
- Monoclonal Plasma Cell proliferation - AL (Ig light chain) is the most common type

Secondary:

• Ongoing Inflammatory process that causes Protein misfolding
  e. g. SAA protein getting secreted in high amounts by the liver and getting improperly degraded so that its amyloid (AA protein) forms

Question 5

What is AL amyloid?

• how does it come about?
• What symptoms might it be associated with?
• Other associations?
• *Primary or Secondary?

Answer 5

AL = Amyloid Light Chain (can be EITHER lambda or kappa)

Cause:
- PLASMA cells have undergone monoclonal proliferation and excess Ab. light chains form amyloid

Symptoms:

• Bence Jones Bodies in the Serum or the Urine
• M protein spike on electrophoresis

Other Associations:

• Concurrent Plasmacytomas may also exist (these are just collections of plamsma cells outside of the bone marrow
• In multiple Myeloma It may be seen Subdermally

**This is a primary Amyloidosis

Question 6

What are some symptoms outside of amyloid deposition that may occur with someone with Light Chain Amyloidosis?

Answer 6

• Ecchymosis and Petecheal lesions due to the excess of antibody
• Don’t forget about Bence Jones bodies in the urine either

Question 7

AA amyloid

• how does it come about?
• What symptoms might it be associated with?
• Other associations?
• *Primary or Secondary?

Answer 7

Amyloid Associated Fibril

How:
- Long Term inflammation mediated by IL-1 and IL-6 promotes SAA secretion from the liver. Deficient breakdown of SAA leads to deposits of SAA that has become AA.

Symptoms:
- Deposition in Liver, Spleen, and Kidney (so I would assume symptoms occur here too)

Other Associations:

• Tuberculosis
• Bronchitis
• AUTOIMMUNE DISEASE
• Chronic Osteomyelitis
• FAMILIAL (inherited) Mediterranean fever

***This is a Secondary Amyloid Disorder

Question 8

Aß amyloid

• how does it come about?
• How does it appear histologically?

Answer 8

**Causes Alzheimer disease

• Aß-amyloid derived from APP (amyloid precursor protein) is deposited in the cerebral BVs

Pathohisto:
- Loose Eosinophilic material that is formed by neurons wrapped around the Aß amyloid

Question 9

Transthyretin (TTR)

• What is it?
• How does it cause amyloidosis?
• Histological Appearance?

Answer 9

Transthyretin (prealbumin) is normally present in the serum to transport thyroxane and Retinol.

Cause:
- Inherited in Familial Amyloid Polyneuropathies (caused by Mutations in the coding sequence)

• OFTEN its found in the heart of old people

Appearance:
- Looks like smooth light pink, acellular chunk in the heart

Question 10

ß2-microglobulin

• what is it?
• How does it cause amyloidosis?
• where is it typically found and in WHO?
• Histological Appearance?

Answer 10

What: 
- ß2-microglobulin chain from the MHC class I protein

Cause:
- Aß2m - fibrinoid version builds up and deposits

Where:
- Found in Synovium and tendon sheaths of Joints

WHO***:
- LONG TERM HEMODIALYSIS patients

HISTO:
- Big Eosinophilic Piece of Gunk in the center of a poorly staining piece of synovium