Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003 Oct 31;302(5646):841. PubMed.

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  1. These two exciting articles provide significant momentum for the field of Parkinson's disease research. The Singleton/Farrer paper cements the role of α-synuclein as a central player in the pathogenesis of PD. Their discovery of an elevated gene dosage effect of the snca gene in the Iowa kindred bears obvious resemblance to the elevated gene dosage of the APP gene conferred by trisomy 21 and its role in the pathogenesis of Alzheimer's disease.

    Omar el Agnaf's work raises many intriguing questions. One, whether α-synuclein levels in body fluids of humans may be used as a biomarker for the disease, and two, as to the precise source of α-synuclein in peripheral blood, which may be platelets. In that sense, el-Agnaf's work also shows intriguing parallels to Alzheimer's disease, as APP isoforms, including of amyloid β-protein, have been found in peripheral blood and CSF. These findings are also of possible relevance to multiple system atrophy, a PD-like illness in which α-synuclein deposits are predominantly found in oligodendroglia, a type of cell that usually does not express significant amounts of the snca gene product.

    View all comments by Michael Schlossmacher

  2. This is a key paper in establishing the role of synuclein and synuclein misfolding in Parkinson disease. It is analagous to the situation in AD, where there is trisomy 21 and, more recently, focal triplications of APP.

    View all comments by David Holtzman

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