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Cerebellar alpha-synuclein levels are decreased in Parkinson's disease and do not correlate with SNCA polymorphisms associated with disease in a Swedish material.

Journal article
Authors Marie Westerlund
Andrea Carmine Belin
Anna Anvret
Anna Håkansson
Hans Nissbrandt
Charlotta Lind
Olof Sydow
Lars Olson
Dagmar Galter
Published in The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume 22
Issue 10
Pages 3509-14
ISSN 1530-6860
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 3509-14
Language en
Links dx.doi.org/10.1096/fj.08-110148
Keywords Aged, Cerebellum, metabolism, Female, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Middle Aged, Parkinson Disease, genetics, metabolism, Polymorphism, Single Nucleotide, Sweden, alpha-Synuclein, genetics, metabolism
Subject categories Physiology

Abstract

Alterations of brain and plasma alpha-synuclein levels and SNCA gene variability have been implicated in the pathogenesis of Parkinson's disease (PD). We therefore measured alpha-synuclein protein levels in postmortem PD and control cerebellum tissue using Western blot and investigated whether the levels correlated to SNCA genotype. We found markedly decreased alpha-synuclein levels in PD patients (n=16) compared to gender- and age-matched controls (n=14; P=0.004) normalized to alpha-tubulin. We also performed an association study of the noncoding polymorphisms rs2737029 (A/G) and rs356204 (A/G) (intron 4), and of rs356219 (T/C) (3'-region) of SNCA in a Swedish PD case-control material. Using a two-sided chi(2) test, we found significant association of rs2737029 (P=0.003; chi(2)=9.07) and rs356204 (P=0.048; chi(2)=3.91) with disease, strengthening the involvement of SNCA polymorphisms in sporadic PD. Stratification of the human postmortem brain material by genotype of the three investigated polymorphisms, did not indicate any influence of genotype on alpha-synuclein protein levels when comparing PD with controls. Taken together, our findings demonstrate that the investigated Parkinson patients have markedly reduced levels of alpha-synuclein in cerebellum, and that this reduction is general, rather then correlated to the investigated polymorphisms, although two of the polymorphisms also associated with disease in a Swedish material.

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