title: Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred.
abstract: Previous genetic analysis of the familial Parkinson's disease Contursi kindred led to the identification of an Ala53Thr pathogenic mutation in the alpha-synuclein gene. We have re-examined one of the original brains from this kindred using new immunohistochemical reagents, thioflavin S staining and immunoelectron microscopy. Surprisingly, we uncovered a dense burden of alpha-synuclein neuritic pathology and rare Lewy bodies. Immunoelectron microscopy demonstrated fibrillar alpha-synuclein-immunoreactive aggregates. Unexpected tau neuritic and less frequent perikaryal inclusions were also observed. Some inclusions were comprised of both proteins with almost complete spatial disparity. We suggest that it is important to recognize that the neurodegenerative process caused by the Ala53Thr mutation in alpha-synuclein is not identical to that seen in typical idiopathic Parkinson's disease brains.
authors.affiliation: Parkinson's Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Pennsylvania, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Duda
authors.forename: Benoit I
authors.initials: BI
authors.lastname: Giasson
authors.forename: Meghann E
authors.initials: ME
authors.lastname: Mabon
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Miller
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Golbe
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000328:Adult; D001109:Archives; D052160:Benzothiazoles; D001921:Brain / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D016253:Microscopy, Immunoelectron; D009410:Nerve Degeneration / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000737:chemistry* / Q000473:pathology / Q000648:ultrastructure; D010300:Parkinson Disease / Q000473:pathology*; D051843:Synucleins; D013844:Thiazoles; D051844:alpha-Synuclein; D016875:tau Proteins / Q000032:analysis*
chemical_list: D052160:Benzothiazoles; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D013844:Thiazoles; D051844:alpha-Synuclein; D016875:tau Proteins; C009462:thioflavin T