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

Amyloid A (AA) amyloidosis is induced by administering amyloid fibrils to animals under inflammatory conditions. Silk fibroin (SF), the main component of silk threads, forms amyloid-like fibrils and has been previously reported to induce AA amyloidosis in mice. In this study, SF was cultured in ethanol solution, and after confirming fibril formation through Thioflavin T assay, Congo red assay, and observation under electron microscopy, cultured SF ethanol solutions were administered to mice via various routes to investigate the induction of target organs and amyloidosis. As a result, cultured SF ethanol solutions were confirmed to reach the lungs and spleen, but no amyloid deposition was observed. While SF forms amyloid-like fibril structures through cultivation in ethanol solution, its amyloid-enhancing factor (AEF) activity is considered low in mice.

Label-free autofluorescence and hyperspectral imaging of cerebral amyloid-ß lesions in aged squirrel monkeys.

The observation of amyloid-ß (Aß) lesions using autofluorescence in transgenic mice and human Alzheimer disease patients has been reported frequently. However, no reports verify the autofluorescence of spontaneous Aß amyloidosis in animals, to our knowledge. We validated the autofluorescence of Aß lesions in spontaneous squirrel monkey cases under label-free conditions; lesions had intense blue-white autofluorescence in fluorescence microscopy using excitation light at 400-440 nm. Thioflavin S staining and immunohistochemistry of the same specimens revealed that this blue-white autofluorescence was derived from Aß lesions. Hyperspectral analysis of these lesions revealed a characteristic spectrum with bimodal peaks at 440 and 460 nm, as reported for Aß lesions in mice. Principal component analysis using hyperspectral data specifically separated the Aß lesions from other autofluorescent substances, such as lipofuscin. A non-labeled and mechanistic detection of Aß lesions by hyperspectral imaging could provide valuable insights for developing early diagnostic techniques.

Local administration of amyloid enhancing factor initiates in situ amyloid A deposition followed by systemic lesions in mice.

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.