title: Initiation and synergistic fibrillization of tau and alpha-synuclein.
abstract: Alpha-synuclein (alpha-syn) and tau polymerize into amyloid fibrils and form intraneuronal filamentous inclusions characteristic of neurodegenerative diseases. We demonstrate that alpha-syn induces fibrillization of tau and that coincubation of tau and alpha-syn synergistically promotes fibrillization of both proteins. The in vivo relevance of these findings is grounded in the co-occurrence of alpha-syn and tau filamentous amyloid inclusions in humans, in single transgenic mice that express A53T human alpha-syn in neurons, and in oligodendrocytes of bigenic mice that express wild-type human alpha-syn plus P301L mutant tau. This suggests that interactions between alpha-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases.
authors.affiliation: Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine.
authors.forename: Benoit I
authors.initials: BI
authors.lastname: Giasson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Forman
authors.forename: Makoto
authors.initials: M
authors.lastname: Higuchi
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Golbe
authors.forename: Charles L
authors.initials: CL
authors.lastname: Graves
authors.forename: Paul T
authors.initials: PT
authors.lastname: Kotzbauer
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001704:Biopolymers; D001923:Brain Chemistry; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000737:chemistry; D009836:Oligodendroglia / Q000737:chemistry; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D051843:Synucleins; D024801:Tauopathies / Q000378:metabolism; D051844:alpha-Synuclein; D016875:tau Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D001704:Biopolymers; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C497604:SNCA protein, human; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein; D016875:tau Proteins