title: Raft lipids as common components of human extracellular amyloid fibrils.
abstract: Amyloid fibrils are fibrillar polypeptide aggregates from several degenerative human conditions, including Alzheimer's and Creutzfeldt-Jakob diseases. Analysis of amyloid fibrils derived from various human diseases (AA, ATTR, Abeta2M, ALlambda, and ALkappa amyloidosis) shows that these are associated with a common lipid component that has a conserved chemical composition and that is specifically rich in cholesterol and sphingolipids, the major components of cellular lipid rafts. This pattern is not notably affected by the purification procedure, and no tight lipid interactions can be detected when preformed fibrils are mixed with lipids. By contrast, the early and prefibrillar aggregates formed in an AA amyloid-producing cell system interact with the raft marker ganglioside-1, and amyloid formation is impaired by addition of cholesterol-reducing agents. These data suggest the existence of common cellular mechanisms in the generation of different types of clinical amyloid deposits.
authors.affiliation: Institut für Molekulare Biotechnologie, Beutenbergstrasse 11, 07745 Jena, Germany.
authors.forename: Gerald P
authors.initials: GP
authors.lastname: Gellermann
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Appel
authors.forename: Astrid
authors.initials: A
authors.lastname: Tannert
authors.forename: Anja
authors.initials: A
authors.lastname: Radestock
authors.forename: Peter
authors.initials: P
authors.lastname: Hortschansky
authors.forename: Volker
authors.initials: V
authors.lastname: Schroeckh
authors.forename: Christian
authors.initials: C
authors.lastname: Leisner
authors.forename: Tim
authors.initials: T
authors.lastname: Lütkepohl
authors.forename: Shmuel
authors.initials: S
authors.lastname: Shtrasburg
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.forename: Mordechai
authors.initials: M
authors.lastname: Pras
authors.forename: Reinhold P
authors.initials: RP
authors.lastname: Linke
authors.forename: Stephan
authors.initials: S
authors.lastname: Diekmann
authors.forename: Marcus
authors.initials: M
authors.lastname: Fändrich
mesh_terms: D000682:Amyloid / Q000032:analysis*; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D002855:Chromatography, Thin Layer; D006801:Humans; D007150:Immunohistochemistry; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D013154:Spleen / Q000378:metabolism
chemical_list: D000682:Amyloid