Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients

Mov Disord. 2006 Oct;21(10):1703-8. doi: 10.1002/mds.21007.

Abstract

Lewy bodies, the pathological hallmark of Parkinson's disease (PD), consist largely of alpha-synuclein, a 14.5-kDa presynaptic neuronal protein implicated in familial PD. An increased copy number and elevated expression of wild-type alpha-synuclein (SNCA) has been shown to cause early-onset familial PD. However, it is not clear whether increased alpha-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 alpha-synuclein expression is associated, among other factors, with the development of sporadic PD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Gene Expression / physiology
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Mesencephalon / metabolism
  • Parkinson Disease / diagnosis
  • Parkinson Disease / genetics*
  • RNA, Messenger / genetics*
  • Reference Values
  • Substantia Nigra / metabolism
  • alpha-Synuclein / genetics*

Substances

  • RNA, Messenger
  • SNCA protein, human
  • alpha-Synuclein