Metabolism of amyloid proteins and methods for detecting amyloid proteins

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Systemic AA amyloidosis is one of the most severe complications of chronic inflammatory disorders, particularly rheumatoid arthritis. It is well known that, similar to an infectious prion protein, amyloid-enhancing factor (AEF) acts as a transmissible agent in AA amyloidosis. However, how AEF transmits AA amyloidosis in vivo remained to be fully elucidated. In the present study, we focused on finding cell-free forms of AEF and its carriers in circulation by using the murine transfer model of AA amyloidosis. We first determined that circulating cell-free AEF existed in blood and plasma in mice with systemic AA amyloidosis. Second, we established that plasma exosomes containing AA amyloid oligomers derived from serum amyloid A had AEF activity and could transmit systemic AA amyloidosis via a prion-like mechanism. These novel findings should provide insights into the transmission mechanism of systemic amyloidoses.We previously reported that two cases of aged vervet monkeys (Cercopithecus … More aethiops) spontaneously developed TTR amyloidosis and showed clinical symptoms mimicking human TTR amyloidosis. However, the pathogenesis of TTR amyloidosis in vervet monkeys and relationship to the human disease remained to be elucidated. The aims of the present study were to elucidate the pathogenesis of TTR amyloidosis in the vervet monkeys, and to verify pathological relationship to the human TTR amyloidosis. First, using over 120 tissue specimens of various primates and clinical cardiac findings of vervet monkeys and crab-eating macaques, we showed that aged vervet monkeys developed TTR amyloidosis mainly causing cardiac dysfunction by means of physicochemical examinations, but other non-human primates showed neither TTR amyloid deposits nor cardiac dysfunctions. Next, we determined that vervet monkeys had the species-specific TTR allele. Taken together, we propose that the aged vervet monkeys mimic the human TTR amyloidosis and the monkey is a precious species as an animal model for this hereditary disease of human. Less