Systemic AA-Amyloidosis in shelter cats

Amyloidosis is a group of protein-misfolding diseases characterize by the deposition of insoluble fibrils in different organs. Several amyloid precursor proteins have been reported in humans and animals. In cats, systemic amyloid A (AA) amyloidosis has been mainly reported in predisposed breeds but only rarely described in domestic short-hair cats. Recently, a high prevalence of the disease has been described in captive cheetahs and its horizontal transmission through feces has been proposed as major contributor. The aims of this research were to investigate the prevalence of systemic AA amyloidosis in shelter cats and to better characterize its histopathological and clinico-laboratory alterations. Liver, kidney, spleen, and bile samples had been collected at cats’ death in three shelters and histopathologic examinations performed. AA amyloidosis was scored and shedding of amyloid fibrils was investigated with western blot in bile. In the three investigated shelters, prevalence of AA amyloidosis was 57.1%, 73.0%, and 52.0%, respectively. Extracted deposits were identified as AA. AA fragments were identified in bile samples raising the possibility of fecal-oral transmission. Renal lesions were evaluated with optical and electron microscopy in nine cats with renal involvement of systemic amyloidosis. Mass spectrometry was used to characterize amyloid. Serum creatinine concentrations were increased in 6 cats and symmetric dimethylarginine was increased in all of the cats, that also had proteinuria. Eight of 9 cats had amyloid in the medulla, and all had amyloid in the cortex (glomeruli) and in the interstitium. Amyloid was AA in each case. Urine protein-to-creatinine (UPC) and urine amyloid A-to-creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate-agarose gel electrophoresis and liquid chromatography-mass spectrometry (LC-MS) of proteins were performed in twenty-nine cats with proteinuria (nineteen with AA amyloidosis with renal involvement). Cats with AA amyloidosis had higher UPC and UAAC ratios than unaffected cats. The LC-MS identified 63 potential biomarkers associated with AA amyloidosis; urine apolipoprotein C-III was higher in cats with AA amyloidosis. The prevalence of systemic AA-amyloidosis is elevated in shelter cats and the cat represents a natural model of systemic AA amyloidosis.