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.
Because of the variety of proteins involved there are many types of amyloid of which a few are:
This is seen in a variety of chronic disease such as rheumatoid arthritis, tuberculosis, bronchiectasis and chronic (usually suppurative) infections from intravenous drug abuse. The commonest protein deposited is serum amyloid protein A, an acute phase protein produced by the liver.
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.
This derives from the immunoglobulin light chains. It is assoicated with the massive overproduction of immunoglobulin from myeloma.
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.
Formed from transthyretin (also known as pre-albumin).
Formed from Cystatin C. Causes hereditary cystatin C amyloid angiopathy, formerly known as hereditary cerebral haemorrhage with amyloidosis-Icelandic or Icelandic CAA.
Gelsolin-derived amyloid. Responsible for familial amyloidosis, Finnish type.
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.)
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. 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.
- ↑ Connolly JO, Gillmore JD, Lachmann HJ, Davenport A, Hawkins PN, Woolfson RG. Renal amyloidosis in intravenous drug users. QJM : monthly journal of the Association of Physicians. 2006 Nov; 99(11):737-42.(Link to article – subscription may be required.)
- ↑ Hawkins PN, Myers MJ, Lavender JP, Pepys MB. Diagnostic radionuclide imaging of amyloid: biological targeting by circulating human serum amyloid P component. Lancet. 1988 Jun 25; 1(8600):1413-8.
- ↑ Pepys MB, Herbert J, Hutchinson WL, Tennent GA, Lachmann HJ, Gallimore JR, Lovat LB, Bartfai T, Alanine A, Hertel C, Hoffmann T, Jakob-Roetne R, Norcross RD, Kemp JA, Yamamura K, Suzuki M, Taylor GW, Murray S, Thompson D, Purvis A, Kolstoe S, Wood SP, Hawkins PN. Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. Nature. 2002 May 16; 417(6886):254-9.(Link to article – subscription may be required.)
- ↑ Gillmore JD, Tennent GA, Hutchinson WL, Gallimore JR, Lachmann HJ, Goodman HJ, Offer M, Millar DJ, Petrie A, Hawkins PN, Pepys MB. Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosis. British journal of haematology. 2010 Mar; 148(5):760-7.(Link to article – subscription may be required.)