α-Synuclein implicated in Parkinson’s disease is present in extracellular biological fluids, including human plasma

Parkinson’s disease (PD) and other related disorders are characterized by the accumulation of fibrillar aggregates of α-synuclein protein (α-syn) inside brain cells. It is likely that the formation of α-syn aggregates plays a seminal role in the pathogenesis of at least some of these diseases, because two different mutations in the gene encoding α-syn have been found in inherited forms of PD. α-Syn is mainly expressed by neuronal cells and is generally considered to exist as a cytoplasmic protein. Here, we report the unexpected identification of α-syn in conditioned culture media from untransfected and α-syn-transfected human neuroblastoma cells, as well as in human cerebrospinal fluid and blood plasma. The method used was immunocapture by using anti-α-syn antibodies coupled to magnetic beads, followed by detection on Western blots. In all cases, α-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 α-syn. Our findings suggest that cells normally secrete α-syn into their surrounding media, both in vitro and in vivo. The detection of extracellular α-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.