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

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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
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

Belin, Andrea CarmineKarolinska Institutet (författare)
Anvret, Anna (författare)
Håkansson, Anna,1978Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xhakan (författare)
Nissbrandt, Hans,1952Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xnisha (författare)
Lind, Charlotta (författare)
Sydow, OlofKarolinska Institutet (författare)
Olson, LarsKarolinska Institutet (författare)
Galter, DagmarKarolinska Institutet (författare)
Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för farmakologi (creator_code:org_t)

Ingår i:The FASEB journal : official publication of the Federation of American Societies for Experimental Biology: Wiley22:10, s. 3509-141530-6860
Ingår i:The FASEB Journal: Wiley22:10, s. 3509-140892-6638

Av författaren/redakt...: Westerlund, Mari ...; Belin, Andrea Ca ...; Anvret, Anna; Håkansson, Anna, ...; Nissbrandt, Hans ...; Lind, Charlotta; visa fler...; Sydow, Olof; Olson, Lars; Galter, Dagmar; visa färre...

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