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Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients

Authors

  • Ornit Chiba-Falek PhD,

    1. Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
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  • Grisel J. Lopez MD,

    1. Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
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  • Robert L. Nussbaum MD

    Corresponding author
    1. Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
    • Genetic Disease Research Branch, National Human Genome Research Institute, NIH, 49 Convent Drive MSC 4472, Bethesda, MD 20892
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Abstract

Lewy bodies, the pathological hallmark of Parkinson's disease (PD), consist largely of α-synuclein, a 14.5-kDa presynaptic neuronal protein implicated in familial PD. An increased copy number and elevated expression of wild-type α-synuclein (SNCA) has been shown to cause early-onset familial PD. However, it is not clear whether increased α-synuclein expression also plays a role in the pathogenesis of sporadic disease. In the current study, we analyzed the levels of SNCA-mRNA in affected brains of sporadic PD patients. We compared the levels of steady state SNCA-mRNA in 7 sporadic PD brain samples and 7 normal controls using real-time polymerase chain reaction of RNA extracted from mid-brain tissue, including the substantia nigra. Despite that there is neuronal loss in the substantia nigra of PD brains, overall the SNCA-mRNA levels were increased in PD brains an average of nearly fourfold over normal control mid-brain, although there was much greater variability in samples from PD patients compared to controls. Frontal cortex samples from selected individuals were also analyzed. SNCA-mRNA levels were not significantly changed in PD frontal cortex compared to controls. These results suggest that elevated expression levels of SNCA-mRNA are found in the affected regions of PD brain and support the hypothesis that increases in α-synuclein expression is associated, among other factors, with the development of sporadic PD. © 2006 Movement Disorder Society

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