Polymorphisms in SAA alter intrarenal amyloid distribution of AA amyloidosis in cats.

The kidneys are one of the primary organs affected by amyloid A (AA) amyloidosis in mixed-breed cats. The distribution of amyloid deposits within the kidneys varies among individuals; however, the underlying cause is unknown. This study investigated the association between serum AA (SAA) polymorphisms and the pattern of renal amyloid deposition in five mixed-breed cats. Histological analysis of the kidneys revealed amyloid deposits in the renal glomeruli and renal papillae in all cases. In contrast, the amyloid deposition pattern differed in the medulla, with widespread deposition from the corticomedullary junctional area to the inner medulla in two of the five cats. These amyloids were mainly located in the basement membrane of the renal tubules, extending towards the lumen and into the interstitium. Conversely, in the other three cats, amyloid deposition in the medulla was sparse and the deposits were localized in the perivascular stroma in the corticomedullary junction. Genetic analysis identified four SAA alleles involving six amino acid substitutions (Q1E, I29K, D42E, Q45R, P48R, and A51V). Mass spectrometry and immunohistochemistry revealed that AA amyloid derived from SAA with Q45 was predominantly deposited in the cortex and papilla, as well as in the perivascular stroma of some parts of the outer medulla. On the other hand, AA amyloid derived from SAA with R45 was specifically observed around the tubules in the renal inner to outer medulla. Except for Q45R, no substitutions were associated with distribution patterns. These findings suggest that the SAA polymorphism sequence is associated with the site of AA amyloid deposition in the kidney. Moreover, this study is the first report of such a complex pattern of amyloid deposition in the organ of the same individual, emphasizing that the primary structure of the amyloid precursor protein determines amyloid distribution.