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Genetic and pathological links between Parkinson's disease and the lysosomal disorder Sanfilippo syndrome
Author(s) -
WinderRhodes Sophie E.,
GarciaReitböck Pablo,
Ban Maria,
Evans Jonathan R.,
Jacques Thomas S.,
Kemppinen Anu,
Foltynie Thomas,
WilliamsGray Caroline H.,
Chinnery Patrick F.,
Hudson Gavin,
Burn David J.,
Allcock Liesl M.,
Sawcer Stephen J.,
Barker Roger A.,
Spillantini Maria Grazia
Publication year - 2012
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.24029
Subject(s) - haplotype , alpha synuclein , pathogenesis , parkinson's disease , pathology , allele , degenerative disorder , lysosomal storage disease , degenerative disease , medicine , disease , biology , genetics , gene
Background: Parkinson's disease (PD) is a common neurodegenerative disorder of unknown etiology. The characteristic α‐synuclein aggregation of PD is also a feature of Sanfilippo syndrome, a storage disorder caused by α‐ 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 α‐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‐α‐synuclein antibody, Per7. Results: Allelic analysis showed an association between rs2071046 and risk for PD ( P 1.3 × 10 −3 ). Intracellular α‐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 α‐synuclein aggregation in the brain in lysosomal storage disorders. Our findings support a mechanism involving lysosomal dysfunction more generally in the pathogenesis of PD. © 2011 Movement Disorder Society