Amyloidosis refers to a group of diseases characterized by abnormal deposition of an insoluble, fibrous, proteinaceous substance (amyloid) in tissue. Amyloid gets its name from the fact that, like starch, it may stain blue with iodine. Amyloid stains intensely with the dye Congo red and shows a green color in polarized light.
Etiology of Amyloidosis in Animals
The precursor proteins in amyloid fibrils may 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. Other precursor molecules may be normal wild-type proteins.
Amyloid may be deposited in localized sites or widely distributed throughout the body. It causes damage by displacing normal cells. If critical organs such as the kidneys, liver, or heart are extensively disrupted, the disease may be fatal.
In humans, at least five forms of amyloidosis have been recognized, characterized by different pathogenesis, clinical syndromes, and amyloidogenic proteins:
AL amyloidosis (amyloid light-chain amyloidosis)
AA amyloidosis (amyloid A amyloidosis)
AF amyloidosis (familial amyloidosis), also referred to as hATTR amyloidosis (hereditary transthyretin amyloidosis)
ATTRwt amyloidosis (transthyretin-related amyloidosis, wild-type), also referred to as senile amyloidosis or age-related amyloidosis
AH amyloidosis (amyloid heavy-chain amyloidosis), which develops in patients on chronic hemodialysis
Only AA, AL, and age-related amyloidosis have been identified in animals.
The most common form of amyloidosis, AA amyloidosis, is generated by misfolding of the major acute-phase protein: serum amyloid A (SAA). SAA concentrations increase substantially in patients, especially dogs, with severe inflammation. In common with other forms of amyloidosis, AA amyloidosis is characterized by codeposition of its amyloidogenic protein and other molecules, including serum amyloid P (SAP), also called pentraxin-2.
If inflammation is persistent, longterm high concentrations of SAA result in the accumulation of AA fibrils in the kidney, spleen, and liver. The C-terminus of SAA folds into a hydrophobic beta sheet that oligomerizes to generate protease-resistant fibrils. Secondary amyloidosis thus develops as a result of chronic inflammatory diseases, such as rheumatoid arthritis; chronic bacterial infections, such as tuberculosis; and some malignant tumors, such as adrenocortical adenomas.
Misfolding of immunoglobulin light chains generates AL amyloidosis. AL amyloidosis commonly results from the overproduction of monoclonal immunoglobulin light chains in patients with plasma cell tumors (myelomas). In AL amyloidosis, amyloid tends to be deposited in mesenchymal tissues, especially nervous tissues and joints.
Some amyloid is formed in all aged animals (age-related amyloidosis). It contains prealbumin fragments that form beta chains.
Some forms of amyloid may even be transmitted between animals. The most important of these are the transmissible spongiform encephalopathies, such as bovine spongiform encephalopathy Bovine Spongiform Encephalopathy and scrapie Scrapie . These are caused by the production of misfolded prion proteins.
Experimental administration of small amounts of amyloid protein to an animal may accelerate development of AA amyloidosis. Cheetahs are especially prone to amyloidosis and shed an infectious form of amyloid protein in their feces.
Epidemiology of Amyloidosis in Animals
Amyloidosis can affect all domestic mammals.
AA amyloidosis is a common cause of death in horses repeatedly immunized for antiserum production.
AL amyloidosis is rare in domestic animals.
Hereditary amyloidoses also occur in animals, including Abyssinian cats and Chinese Shar-Pei dogs.
Minor subclinical deposition of amyloid proteins is common in aged animals.
Clinical Findings of Amyloidosis in Animals
Clinical signs of amyloidosis vary, depending upon their location and which organs are affected.
If AA amyloid is deposited in organs, such as the spleen, it may not cause clinical signs. If, however, the kidneys are involved, the presence of AA amyloid in glomeruli may lead to severe proteinuria, eventually resulting in renal failure and death.
In age-related amyloidosis, amyloid is commonly deposited in the media of meningeal and cortical arteries.
Tumorlike 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.
Diagnosis of Amyloidosis in Animals
Because of its diffuse distribution and insidious onset, amyloidosis may be difficult to diagnose clinically.
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. Measurements of SAA concentrations are of limited usefulness.
Treatment of Amyloidosis in Animals
There is no specific treatment that can prevent the development of amyloidosis or promote the resorption of amyloid fibrils.
In AA amyloidosis, although there is no practical treatment, elimination of the source of the chronic inflammation may slow amyloid deposition and hence progression of the disease. 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; however, the most important ones are chronic persistent inflammatory diseases and cancers.
Amyloidosis may be difficult to diagnose on the basis of clinical signs because these will depend on the location and the organs affected.
Localized superficial amyloid nodules may be removed surgically. Treatment of systemic amyloidosis depends on identifying and eliminating the cause of the underlying inflammation.
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