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So named as staining pattern with iodine resembles that of starch.[1]

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 systemic amyloid from whatever primary cause 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 degradation. 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.

Amyloid showing positive Congo Red staining and birefringence (alternating frames).



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.[2] The commonest protein deposited is serum amyloid protein A, an acute phase protein produced by the liver.

2M 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 associated with the massive overproduction of immunoglobulin from myeloma or B cell dyscrasias. At least 65% of systemic amyloidosis presentations in Western Europe and the USA are due to this.

AH amyloid

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

ATTR amyloid

As a cause of systemic amyloidosis (i.e. outside the cerebral circulation), ATTR amyloid is divided into the hereditary form (TTRm = TTR mutated) and the wild-type form (TTRwt = TTR wild type). The TTRwt form typically occuring in elderly males and is sometimes termed senile systemic amyloidosis, although a predilection for cardiac involvement is common. ATTRwt may be difficult to distinguish from AL amyloid if the patient also has a plasma cell dyscrasia.

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.


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.[3] SAP is initially distributed to organs receiving a rich blood supply, but also associates with existing amyloid deposits.

Certain organs may show characteristic imaging, e.g. a speckled appearance on cardiac ultrasound may strongly suggest amyloid infiltration.

Amyloid typically deposits around vessels.
Another example of amyloid within the vessel wall.

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.


CPHPC, a drug that targets and depletes SAP, appears to be a promising treatment.[4][5]

In an animal model, monoclonal antibodies targetting the SAP component may elicit a sufficient destructive inflammatory response to remove the amyloid deposits.[6]. Human studies, currently at phase I, are being undertaken.[7] Monoclonal antibodies against amyloid itself are also being employed, e.g. NEOD001 targets AL amyloid.[8]


  1. Virchow R. Über eine im Gehirn und Ruckenmark des Menschen aufgefunde Substanz mit der chemishen Reaction der Cellulose. Virchows Arch Path Anat. 1854;6:135–8.
  2. 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.)
  3. 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.
  4. 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.)
  5. 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.)
  6. Bodin K, Ellmerich S, Kahan MC, Tennent GA, Loesch A, Gilbertson JA, Hutchinson WL, Mangione PP, Gallimore JR, Millar DJ, Minogue S, Dhillon AP, Taylor GW, Bradwell AR, Petrie A, Gillmore JD, Bellotti V, Botto M, Hawkins PN, Pepys MB. Antibodies to human serum amyloid P component eliminate visceral amyloid deposits. Nature. 2010 Nov 4; 468(7320):93-7.(Link to article – subscription may be required.)
  7. Richards DB, Cookson LM, Berges AC, Barton SV, Lane T, Ritter JM, Fontana M, Moon JC, Pinzani M, Gillmore JD, Hawkins PN, Pepys MB. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. The New England journal of medicine. 2015 Sep 17; 373(12):1106-14.(Link to article – subscription may be required.)
  8. Gertz MA, Landau H, Comenzo RL, Seldin D, Weiss B, Zonder J, Merlini G, Schönland S, Walling J, Kinney GG, Koller M, Schenk DB, Guthrie SD, Liedtke M. First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Feb 8.(Epub ahead of print) (Link to article – subscription may be required.)