Amyloidosis

In medicine, amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues, causing disease. A protein is amyloid if, due to an alteration in its secondary structure, it takes on a particular insoluble form, called the beta-pleated sheet.

Approximately 25 different proteins are known that can form amyloid in humans. Most of them are constituents of the plasma.

Different amyloidoses can be systemic (affecting many different organ systems) or organ-specific. Some are inherited, due to mutations in the precursor protein. Other, secondary forms are due to different diseases causing overabundant or abnormal protein production-such as with over production of immunoglobulin light chains in multiple myeloma (termed AL amyloid), or with continuous overproduction of acute phase proteins in chronic inflammation (which can lead to AA amyloid).

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Diagnosis

Amyloid can be diagnosed on histological examination of affected tissue. Amyloid deposits can be identified histologically by Congo red staining and viewing under polarized light where amyloid deposits produce a distinctive 'apple green birefringence'. Further, specific, tests are available to more precisely identify the amyloid protein. Biopsies are taken from affected organs (for example, the kidney), or often in the case of systemic amyloid, from the rectum or anterior abdominal adipose tissue. In addition, all amyloid deposits contain serum amyloid P component (SAP), a circulating protein of the pentraxin family. Radionuclide SAP scans have been developed which can anatomically localize amyloid deposits in patients.

Systemic amyloidosis

Primary/Hereditary amyloidosis

These rare hereditary disorders are usually due to point mutations in precursor proteins, and are also usually autosomal dominantly transmitted.The precursor proteins are;

• transthyretin - the most commonly implicated protein.
• lysozyme
• apolipoprotein B
• fibrinogen
• apolipoprotein A1
• gelsolin

Secondary amyloidosis

These are far more common than the primary amyloidoses.

• AL amyloidosis (immunoglobulin light chains are the precursor protein, overproduced in multiple myeloma). This is sometimes, confusingly and erroneously, called 'primary amyloidosis'.
• AA amyloidosis (the precursor protein is serum amyloid A protein (SAA), an acute-phase protein due to chronic inflammation). In contrast to AL amyloid, this has previously been termed 'secondary amyloidosis' .These occur with a wide variety of diseases associated with chronic inflammation, such as rheumatoid arthritis, familial mediterranean fever or chronic infection.
• Dialysis related amyloidosis (the precursor protein is beta-2-microglobulin which is not removed with dialysis, and thus accumulates in patients with end stage renal failure on dialysis).^[1]

Organ-specific amyloidosis

In almost all of the organ-specific pathologies, there is significant debate as to whether the amyloid plaques are the causal agent of the disease or instead a downstream consequence of a common idiopathic agent. The associated proteins are indicated in parentheses.

Neurological amyloid

• Alzheimer's disease (Aβ 39-43)
• Parkinson's disease (alpha-synuclein)
• Huntington's disease (huntingtin)
• Transmissible spongiform encephalopathies caused by prion protein (PrP) were sometimes classed as amyloidoses, as one of the four pathological features in diseased tissue is the presence of amyloid plaques. These diseases include;
  • Creutzfeldt-Jakob disease (PrP in cerebrum)
  • Kuru (diffuse PrP deposits in brain)
  • Fatal Familial Insomnia (PrP in thalamus)
  • Bovine spongiform encephalopathy (PrP in cerebrum of cows)

Cardiovascular amyloid

• Cardiac amyloidosis
  • Senile cardiac amyloidosis-may cause heart failure
• Congophilic angiopathy

Other

• Amylin deposition can occur in the pancreas in some cases of type 2 diabetes mellitus

Famous People who have contracted Amyloidosis

• James Oliver Rigney, Jr. (aka. Robert Jordan)
• David Lange

References

1. ^ Uremia, Timothy W. Meyer and Thomas H. Hostetter, N Engl J Med, 2007 Sep 27, 357(16):1316