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Genetic and pathological links between Parkinson's disease and the lysosomal disorder Sanfilippo syndrome

Lookup NU author(s): Professor Patrick Chinnery, Professor Gavin Hudson, Professor David Burn, Dr Liesl Allcock


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Background: Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. The characteristic a-synuclein aggregation of PD is also a feature of Sanfilippo syndrome, a storage disorder caused by a-N-acetylglucosaminidase (NAGLU) gene mutations. We explored genetic links between these disorders and studied the pathology of Sanfilippo syndrome to investigate a common pathway toward a-synuclein aggregation. Methods: We typed the 2 single-nucleotide polymorphisms that tag the common haplotypes of NAGLU in 926 PD patients and 2308 controls and also stained cortical tissue from 2 cases of Sanfilippo A syndrome using the anti-a-synuclein antibody, Per7. Results: Allelic analysis showed an association between rs2071046 and risk for PD (P 1.3 x 10(-3)). Intracellular alpha-synuclein accumulation was observed in the cortical tissue of both Sanfilippo A syndrome cases. Conclusions: This study suggests a possible role of NAGLU in susceptibility to PD while extending evidence for a-synuclein aggregation in the brain in lysosomal storage disorders. Our findings support a mechanism involving lysosomal dysfunction more generally in the pathogenesis of PD. (C) 2011 Movement Disorder Society

Publication metadata

Author(s): Winder-Rhodes SE, Garcia-Reitbock P, Ban M, Evans JR, Jacques TS, Kemppinen A, Foltynie T, Williams-Gray CH, Chinnery PF, Hudson G, Burn DJ, Allcock LM, Sawcer SJ, Barker RA, Spillantini MG

Publication type: Article

Publication status: Published

Journal: Movement Disorders

Year: 2012

Volume: 27

Issue: 2

Pages: 312-315

Print publication date: 18/11/2011

ISSN (print): 0885-3185

ISSN (electronic): 1531-8257

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/mds.24029


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Funder referenceFunder name
NIHR Biomedical Research Centre
PPP Healthcare Foundation
University of Cambridge
University of Cambridge and Parkinson's UK
068545/Z/02Wellcome Trust
G0000934Medical Research Council