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Amyloidosis: Introduction |  |
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Amyloidoses are protein misfolding diseases. When new proteins are made, they normally fold automatically into their correct configuration. Sometimes, however, mistakes are made and incorrectly folded protein gets deposited in tissues. This misfolded protein consisting of very stable β-sheets is called amyloid. Amyloid may be deposited in a localized fashion or may be widely distributed throughout the body. It causes 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. |
| Many different proteins can misfold, and amyloidosis can be classified on the basis of these fibril proteins. The most common form of amyloid is generated by misfolding of the acute-phase protein, serum amyloid A. Its misfolded product, AA amyloid, 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 commonly deposited in
parenchymal organs and may not cause clinical signs. The spleen is commonly affected. If the kidneys are involved, the presence of amyloid in glomeruli may lead to proteinuria, eventually resulting in renal failure. |
| A second common form of amyloid, AL amyloid, is generated by misfolding of immunoglobulin light chains. Its deposition results from the overproduction of monoclonal light chains in animals with multiple myeloma. It tends to be deposited in mesenchymal tissues, especially nervous tissues and joints. |
| At least 20 other proteins have been shown to misfold 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 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. Localized deposits of amyloid are not uncommon, and it is believed that they result
from the local production of fibril precursors. 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 (
Bovine Spongiform Encephalopathy: Introduction) and scrapie (
Scrapie: Introduction). These are caused by misfolded prion proteins. Indeed, there is evidence that AA amyloid is somewhat transmissible; experimental administration of small amounts of amyloid protein to an animal has been shown to accelerate its development. |
| 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 conditions such as chronic abscesses or multiple myeloma should be treated to reduce the availability of fibril precursor
protein. Amyloidosis is readily recognized at necropsy and in histologic sections by its affinity for Congo red dye. |
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