Raft lipids as common components of human extracellular amyloid fibrils.
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.
Gellermann
Gerald P
GP
Institut für Molekulare Biotechnologie, Beutenbergstrasse 11, 07745 Jena, Germany.
Appel
Thomas R
TR
Tannert
Astrid
A
Radestock
Anja
A
Hortschansky
Peter
P
Schroeckh
Volker
V
Leisner
Christian
C
Lütkepohl
Tim
T
Shtrasburg
Shmuel
S
Röcken
Christoph
C
Pras
Mordechai
M
Linke
Reinhold P
RP
Diekmann
Stephan
S
Fändrich
Marcus
M
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
D000682:Amyloid