Divergent renal localization patterns of heterozygote-derived two distinct AA amyloids in a cat

Abstract

Abstract Amyloid A (AA) amyloidosis poses a fatal threat to both humans and animals. While the kidneys represent the principal organ affected in AA amyloidosis, there exists variability in the localization of amyloid deposition, with distinct symptoms delineated by the specific deposition sites. Nevertheless, the factors contributing to the diversity of deposition remain unclear. In this study, we identified an association between serum amyloid A (SAA) polymorphisms and patterns of amyloid deposition. Histopathological analysis of the kidneys from a 5-year-old spayed female Japanese cat, which succumbed to systemic AA amyloidosis, revealed renal amyloid deposition in cortical glomeruli and medullary interstitium. Genetic analysis disclosed that the afflicted cat possessed a heterozygous SAA with three amino acid substitutions (K47I, Q63R, S93N), resulting in the SAAKQS and SAAIRN variants. Mass spectrometry and immunohistochemistry demonstrated that SAAKQS was deposited in the glomerulus and renal papilla, while SAAIRN was restricted to the extramedullary zone. This study established the differing renal distributions of two AA amyloid variants originating from heterozygotes within a single individual. The evidence supports the notion that the primary structure of precursor proteins defines the distribution of amyloid deposition.