Alpha-synuclein implicated in Parkinson's disease is present in extracellular biological fluids, including human plasma

FASEB J. 2003 Oct;17(13):1945-7. doi: 10.1096/fj.03-0098fje. Epub 2003 Aug 15.


Parkinson's disease (PD) and other related disorders are characterized by the accumulation of fibrillar aggregates of alpha-synuclein protein (alpha-syn) inside brain cells. It is likely that the formation of alpha-syn aggregates plays a seminal role in the pathogenesis of at least some of these diseases, because two different mutations in the gene encoding alpha-syn have been found in inherited forms of PD. alpha-Syn is mainly expressed by neuronal cells and is generally considered to exist as a cytoplasmic protein. Here, we report the unexpected identification of alpha-syn in conditioned culture media from untransfected and alpha-syn-transfected human neuroblastoma cells, as well as in human cerebrospinal fluid and blood plasma. The method used was immunocapture by using anti-alpha-syn antibodies coupled to magnetic beads, followed by detection on Western blots. In all cases, alpha-syn was identified as a single 15 kDa band, which co-migrated with a recombinant form of the protein and reacted with five different antibodies to alpha-syn. Our findings suggest that cells normally secrete alpha-syn into their surrounding media, both in vitro and in vivo. The detection of extracellular alpha-syn and/or its modified forms in body fluids, particularly in human plasma, offers new opportunities for the development of diagnostic tests for PD and related diseases.

MeSH terms

  • Blotting, Western
  • Extracellular Space / chemistry
  • Humans
  • Models, Biological
  • Nerve Tissue Proteins / analysis*
  • Nerve Tissue Proteins / blood
  • Nerve Tissue Proteins / cerebrospinal fluid
  • Neurons / metabolism
  • Parkinson Disease / etiology
  • Synucleins
  • Tumor Cells, Cultured
  • alpha-Synuclein


  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein