Amyloid

From Ganfyd

Rather than a specific protein, amyloid is a state that many proteins may fall or be precipitated into, the alpha-helix collapsing into the more stable (lower energy) beta-sheet. This is visible only on x-ray diffraction. On electron microscopy, amyloid has a characteristic fibrillar structure.

Serum amyloid P component appears to be an integral part of amyloid and is thought to either contribute to formation and/or persistence of amyloid deposits. The resulting amyloid deposits are very stable and appear to resist degradataion. This is the same reason why silk is considered non-absorbable as it is also formed from β-pleated sheets.

Amyloid deposition may be local, for example in Alzheimer's disease or it may be systemic.

There are several named types of amyloid. The construct is Ax (where A refers to amyloid and x refers to the protein deposited. Prion diseases can also be associated with protein deposition that is amyloid-like.

Types

Because of the variety of proteins involved there are many types of amyloid of which a few are:

AA amyloid

This is seen in a variety of chronic disease such as rheumatoid arthritis, tuberculosis, bronchiectasis and chronic (usually suppurative) infections from intravenous drug abuse.^[1] The commonest protein deposited is serum amyloid protein A, an acute phase protein produced by the liver.

Aβ₂M amyloid

This is associated with haemodialysis and rarely with renal failure patients not on dialysis. It forms because β₂ microglobulin (part of the MHC molecule) is small enough not to be removed by dialysis. It would normally be broken down in the kidney.

AL amyloid

This derives from the immunoglobulin light chains. It is assoicated with the massive overproduction of immunoglobulin from myeloma.

AH amyloid

Is deposition of immunoglobulin heavy chains. It is a rare form of amyoid and only a few cases have ever been reported.

Cerebral Amyloid Angiopathy

See main article. Several types of mutations, either occuring sporadically or inherited, can result in deposition of amyloid in vessels. This can lead to brain haemorrhage.

Amyloid beta A4 protein

Aβ from abnormal processing of APP in Alzheimer's disease

ATTR amyloid

Formed from transthyretin (also known as pre-albumin).

ACys amyloid

Formed from Cystatin C. Causes hereditary cystatin C amyloid angiopathy, formerly known as hereditary cerebral haemorrhage with amyloidosis-Icelandic or Icelandic CAA.

AGel amyloid

Gelsolin-derived amyloid. Responsible for familial amyloidosis, Finnish type.

Complications

Amyloid deposits destroy organ function. This is commonly seen in the deterioration of renal function. The expansion of organ size can also cause pressure effects on surrounding structures, e.g. increase in flexor retinaculum leading to carpal tunnel syndrome.)

Diagnosis

Amyloid can be identified via scintigraphy. Serum amyloid P component (SAP) labelled with radio-iodine (I-123) is administered and a whole body scintigraphic image is obtained.^[2] SAP is initially distributed to organs receiving a rich blood supply, but also associates with existing amyloid deposits.

Histologically, amyloid stains red with Congo Red staining and, when viewed under polarised light, exhibits characteristic birefringence (can be yellow, green, blue, but classically 'apple green'). Staining with Thioflavin T and subsequent fluorescence microscopy is an alternative method of detection.

Treatment

CPHPC, a drug that targets and depletes SAP, appears to be a promising treatment.^[3][4]

References