HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: fj.08-110148v1 22/10/3509    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Westerlund, M. Articles by Galter, D. Search for Related Content PubMed PubMed Citation Articles by Westerlund, M. Articles by Galter, D.

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

Marie Westerlund^*, Andrea Carmine Belin^*, Anna Anvret^*, Anna Håkansson, Hans Nissbrandt, Charlotta Lind, Olof Sydow, Lars Olson^* and Dagmar Galter^*,1

^* Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden;

Department of Pharmacology, Sahlgrenska Academy at Göteborg University, Göteborg, Sweden; and

Department of Clinical Neuroscience, Neurology Section, Karolinska University Hospital, Stockholm, Sweden

¹Correspondence: Department of Neuroscience, Retzius väg 8, Karolinska Institutet, 171 77 Stockholm, Sweden. E-mail: dagmar.galter{at}ki.se

Alterations of brain and plasma -synuclein levels and SNCA gene variability have been implicated in the pathogenesis of Parkinson’s disease (PD). We therefore measured -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 -synuclein levels in PD patients (n=16) compared to gender- and age-matched controls (n=14; P=0.004) normalized to -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 ² test, we found significant association of rs2737029 (P=0.003; ²=9.07) and rs356204 (P=0.048; 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 -synuclein protein levels when comparing PD with controls. Taken together, our findings demonstrate that the investigated Parkinson patients have markedly reduced levels of -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.—Westerlund, M., Belin, A. C., Anvret, A., Håkansson, A., Nissbrandt, H., Lind, C., Sydow, O., Olson, L., and Galter, D. Cerebellar -synuclein levels are decreased in Parkinson’s disease and do not correlate with SNCA polymorphisms associated with disease in a Swedish material.

Key Words: NACP • PARK1 • PD1 • Western blot