Amyloidoses are diseases that result from errors in protein folding. When new proteins are made, their peptide chains normally fold automatically into the correct shape. Sometimes, however, these peptide chains fold incorrectly to form highly stable β-sheets that are very insoluble and resistant to proteolytic digestion. This insoluble protein is deposited in tissues where it is called amyloid. Amyloid proteins may be deposited in a localized fashion or widely distributed throughout the body. They cause damage by displacement of normal cells. If critical organs such as the kidneys, liver, or heart are involved, the disease may be fatal. Amyloidosis can affect all domestic mammals, and minor, asymptomatic deposition of amyloid is common in aged animals.
The most common form of amyloid is generated by misfolding of the acute-phase protein, serum amyloid A (SAA). Levels of SAA in the blood climb significantly in animals with severe inflammation. This provides a source of misfolded protein called AA amyloid. Amyloidosis thus develops as a sequela of chronic inflammatory diseases, chronic bacterial infections, and malignant tumors. It is a common cause of death in horses aggressively immunized for antiserum production. AA amyloid is deposited in parenchymal organs where it may not cause clinical signs. The spleen is commonly affected. If the kidneys are involved, the presence of amyloid in glomeruli may lead to major proteinuria, eventually resulting in renal failure and death. There is no practical treatment for this form of amyloidosis, although removal of the source of inflammation may slow progression of the disease.
Misfolding of immunoglobulin light chains generates a second form of amyloid, AL amyloid. It results from the overproduction of monoclonal light chains in animals with multiple myeloma. AL amyloid tends to be deposited in mesenchymal tissues, especially nervous tissues and joints. It is rare in domestic animals.
At least 20 other proteins are known to misfold, form β-sheets, and become deposited in the tissues as amyloid. Thus, there are many recognized forms of hereditary amyloidoses, such as those described in Abyssinian cats and Chinese Shar-Pei dogs. Some amyloid is formed in all aged animals (senile systemic amyloidosis); eg, in aged dogs, amyloid is commonly deposited in the media of meningeal and cortical arteries. Tumor-like amyloid nodules and subcutaneous amyloid have been reported in horses.
Some forms of amyloid are transmissible. The most important of these are the transmissible spongiform encephalopathies, such as bovine spongiform encephalopathy (see Bovine Spongiform Encephalopathy) and scrapie (see Scrapie). These are caused by misfolded prion proteins. Indeed, AA amyloid is somewhat transmissible, because experimental administration of small amounts of amyloid protein to an animal can accelerate its development. Cheetahs are especially prone to amyloidosis and have been shown to shed an infectious form of amyloid protein in their feces.
Because of its diffuse distribution and insidious onset, amyloidosis is difficult to diagnose clinically. However, amyloidosis should be suspected if renal or hepatic failure develops in animals with chronic infections or inflammation. There is no specific therapy that can prevent the development of amyloidosis or promote the resorption of fibrils. Animals with chronic abscesses or multiple myeloma should be treated to reduce the availability of SAA. Amyloidosis is readily recognized at necropsy and in histologic sections by its affinity for dyes such as Congo red.
Last full review/revision March 2012 by Ian Tizard, BVMS, PhD, DACVM