Amyloidosis in Animals
Amyloidoses are characterized by the deposition of insoluble proteins in tissues. Amyloids are very stable proteins that result from errors in protein folding. When proteins are synthesized, their peptide chains normally fold into the correct shape. Sometimes, however, the peptide chains fold incorrectly and form highly stable insoluble beta sheets that are resistant to proteolytic digestion and cannot be degraded. When this insoluble protein is deposited in tissues, it is called amyloid. It gets its name from the fact that, like starch, it may stain blue with iodine. Amyloid proteins stain intensely with the dye Congo red and show a green color in polarized light. Amyloid proteins may be deposited in localized sites or widely distributed throughout the body. They cause damage by displacing normal cells. If critical organs such as the kidneys, liver, or heart are extensively disrupted, the disease may be fatal. Amyloidosis can affect all domestic mammals, and minor, asymptomatic deposition of amyloid proteins is common in aged animals.
The most common form of amyloid is generated by misfolding of the major acute-phase protein, serum amyloid A (SAA). Levels of SAA in the blood climb significantly in animals with severe inflammation. If SAA fails to fold correctly, it forms a very stable protein called AA amyloid. Amyloidosis thus develops as a result of chronic inflammatory diseases, chronic bacterial infections such as tuberculosis, and some malignant tumors such as adrenocortical adenomas. AA amyloidosis is a common cause of death in horses repeatedly immunized for antiserum production. AA amyloid is usually deposited in organs, such as the spleen, where it may not cause clinical signs. If the kidneys are involved, the presence of amyloid in glomeruli may lead to severe proteinuria, eventually resulting in renal failure and death. There is no practical treatment for this form of amyloidosis, although elimination of the source of inflammation may slow amyloid deposition and hence progression of the disease.
Misfolding of immunoglobulin light chains generates a second form of amyloid, AL amyloid. This commonly results from the overproduction of monoclonal immunoglobulin light chains in animals with plasma cell tumors (myelomas). AL amyloid tends to be deposited in mesenchymal tissues, especially nervous tissues and joints. It is rare in domestic animals.
In humans, at least five different forms of amyloid have been recognized. In addition to AA and AL, AF amyloid develops in an inherited form of the disease; AS amyloid develops in aged individuals; and AH amyloid develops in patients on chronic hemodialysis. Only AA, AL, and AS have been identified in animals.
Hereditary amyloidoses also occur in animals, including Abyssinian cats and Chinese Shar-Pei dogs. Some amyloid is formed in all aged animals (AS amyloid). It contains prealbumin fragments that form beta chains. AS amyloid is commonly deposited in the media of meningeal and cortical arteries. Tumor-like amyloid nodules and subcutaneous amyloid have been reported in horses. These nodules commonly develop in the skin and respiratory tract and appear to be predominantly of the AL type.
Some forms of amyloid may be transmitted between animals. The most important of these are the transmissible spongiform encephalopathies, such as bovine spongiform encephalopathy and scrapie. These are caused by the production of misfolded prion proteins. Indeed, even AA amyloid is somewhat transmissible, because experimental administration of small amounts of amyloid protein to an animal may accelerate its development. Cheetahs are especially prone to amyloidosis and shed an infectious form of amyloid protein in their feces.
Because of its diffuse distribution and insidious onset, amyloidosis may be difficult to diagnose clinically. Clinical signs depend upon their location and which organs are affected. The localized nodular form in horses may be identified by biopsy of the nodules, and these may be removed surgically. However, systemic amyloidosis should be suspected if progressive renal or hepatic failure develops in animals subsequent to chronic infections or inflammation. Amyloidosis is readily recognized at both biopsy and necropsy and in histologic sections by its affinity for dyes such as Congo red.
There is no specific therapy that can prevent the development of amyloidosis or promote the resorption of fibrils. Progression can be delayed by reducing inflammation, so if amyloidosis is confirmed by biopsy, the veterinarian must determine the cause. Animals with persistent inflammatory lesions should be given appropriate treatment. Likewise, the presence of tumors should be identified and treated if possible.
There are multiple causes of amyloidosis, but the most important ones are chronic inflammatory lesions and cancers.
Amyloidosis may be difficult to diagnose on the basis of clinical signs because these will depend upon the location and the organs affected.
Localized superficial amyloid nodules may be removed surgically. Treatment of systemic amyloidosis depends upon identifying and eliminating the underlying cause.