title: 100 years of Lewy pathology.
abstract: In 1817, James Parkinson described the symptoms of the shaking palsy, a disease that was subsequently defined in greater detail, and named after Parkinson, by Jean-Martin Charcot. Parkinson expected that the publication of his monograph would lead to a rapid elucidation of the anatomical substrate of the shaking palsy; in the event, this process took almost a century. In 1912, Fritz Heinrich Lewy identified the protein aggregates that define Parkinson disease (PD) in some brain regions outside the substantia nigra. In 1919, Konstantin Nikolaevich Tretiakoff found similar aggregates in the substantia nigra and named them after Lewy. In the 1990s, α-synuclein was identified as the main constituent of the Lewy pathology, and its aggregation was shown to be central to PD, dementia with Lewy bodies, and multiple system atrophy. In 2003, a staging scheme for idiopathic PD was introduced, according to which α-synuclein pathology originates in the dorsal motor nucleus of the vagal nerve and progresses from there to other brain regions, including the substantia nigra. In this article, we review the relevance of Lewy's discovery 100 years ago for the current understanding of PD and related disorders.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. mg@mrc-lmb.cam.ac.uk
authors.forename: Michel
authors.initials: M
authors.lastname: Goedert
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
authors.forename: Kelly
authors.initials: K
authors.lastname: Del Tredici
authors.forename: Heiko
authors.initials: H
authors.lastname: Braak
mesh_terms: D001921:Brain / Q000473:pathology*; D005858:Germany; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D020961:Lewy Body Disease / Q000266:history*; D019578:Multiple System Atrophy / Q000266:history*; D010300:Parkinson Disease / Q000266:history*; D051844:alpha-Synuclein / Q000266:history*
chemical_list: D051844:alpha-Synuclein