title: Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies.
abstract: Lewy bodies (LBs) are hallmark lesions of degenerating neurons in the brains of patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recently, a point mutation in the gene encoding the presynaptic alpha-synuclein protein was identified in some autosomal-dominantly inherited familial PD pedigrees, and light microscopic studies demonstrated alpha-synuclein immunoreactivity in LBs of sporadic PD and DLB. To characterize alpha-synuclein in LBs, we raised monoclonal antibodies (MAbs) to LBs purified from DLB brains and obtained a MAb specific for alpha-synuclein that intensely labeled LBs. Light and electron microscopic immunocytochemical studies performed with this MAb as well as other antibodies to alpha-and beta-synuclein showed that alpha-synuclein, but not beta-synuclein, is a component of LBs in sporadic PD and DLB. Western blot analyses of highly purified LBs from DLB brains showed that full-length as well as partially truncated and insoluble aggregates of alpha-synuclein are deposited in LBs. Thus, these data strongly implicate alpha-synuclein in the formation of LBs and the selective degeneration of neurons in sporadic PD and DLB.
authors.affiliation: Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Baba
authors.forename: S
authors.initials: S
authors.lastname: Nakajo
authors.forename: P H
authors.initials: PH
authors.lastname: Tu
authors.forename: T
authors.initials: T
authors.lastname: Tomita
authors.forename: K
authors.initials: K
authors.lastname: Nakaya
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: T
authors.initials: T
authors.lastname: Iwatsubo
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism; D003704:Dementia / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D051843:Synucleins; D014452:Ubiquitins / Q000378:metabolism; D051844:alpha-Synuclein; D051846:beta-Synuclein
chemical_list: D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; C497607:SNCB protein, human; D051843:Synucleins; D014452:Ubiquitins; D051844:alpha-Synuclein; D051846:beta-Synuclein