Local administration of amyloid enhancing factor initiates <i>in situ</i> amyloid A deposition followed by systemic lesions in mice

Abstract

Amyloid A (AA) amyloidosis is experimentally transmissible in some animal species, such as mice and chickens. While the spleen is important as the initial deposition site in the transmission of AA amyloidosis, it is not essential for establishing the transmission, and its role is not precisely understood. In this study, to clarify why the spleen is the first site of deposition in transmissible AA amyloidosis, we administered amyloid enhancing factor, which is AA fibrils extracted from AA amyloidosis affected mouse to local organs (liver, spleen, kidney, stomach wall, and Peyer’s patches), to tail vein and into peritoneum; then compared the amyloid distribution. Interestingly, initial amyloid deposition was observed at the administration site in each administered organ, not just the spleen. Furthermore, the amount of amyloid deposition in intra-organ administration groups was larger than that of the intravenous or intraperitoneal administration groups. This study indicates that locally exposed AEF initiates in situ amyloid deposition, from which amyloid deposition spreads throughout the body.

Fibrinogen Aα‐chain amyloidosis outbreaks in Japanese squirrels (Sciurus lis): a potential disease model

“…In addition, four cases developed AFib and AA deposits in the glomeruli and tubular interstitium, respectively (double amyloidosis). In rodents, such as mice [35] and guinea pigs [36], AA deposition is more prominent in the tubular interstitium than in the glomeruli. In the present study, AA depositions were also found in the tubulointerstitium but not in the glomeruli.…”

“…White means no peptides were detected. The maximum numbers of detected peptides in each Japanese squirrel (shown in red) were23,23, 42,11, 58,31, 94,32,28,28,28,19,35,28,31,32, and 22, respectively. There were no C-terminal peptides detected after Glu567 in any of the cases.…”

Studies on the potential risk of amyloidosis from exposure to cultured fibril from silk fibroin

“…There were no amyloid deposits in Experiment 4 despite intravenous administration of SF in ethanol to mice; therefore, we considered the possibility of amyloid deposits occurring through direct splenic administration, which is more conducive to amyloid deposition [20]. No amyloid deposition was observed in any of the groups.…”