title: Transmission of circulating cell-free AA amyloid oligomers in exosomes vectors via a prion-like mechanism.
abstract: Recent studies clearly demonstrated that several types of pathogenic amyloid proteins acted as agents that could transmit amyloidosis by means of a prion-like mechanism. 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.
authors.affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tasaki
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Ueda
authors.forename: Sho
authors.initials: S
authors.lastname: Ochiai
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Sho
authors.initials: S
authors.lastname: Murata
authors.forename: Yohei
authors.initials: Y
authors.lastname: Misumi
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.forename: Xuguo
authors.initials: X
authors.lastname: Sun
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinriki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.forename: Makoto
authors.initials: M
authors.lastname: Shono
authors.forename: Konen
authors.initials: K
authors.lastname: Obayashi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000686:Amyloidosis / Q000097:blood / Q000378:metabolism*; D000818:Animals; D055354:Exosomes / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011328:Prions / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D011328:Prions; D000685:Serum Amyloid A Protein; C046748:amyloid enhancing factor