Parkinson's disease (PD) is characterized by the presence of Lewy bodies containing phosphorylated and aggregated alpha-synuclein (alpha-syn). alpha-Syn is present in human body fluids, including blood plasma, and is a potential biomarker for PD. Immunoassays for total and oligomeric forms of both normal and phosphorylated (at Ser-129) alpha-syn have been used to assay plasma samples from a longitudinal cohort of 32 patients with PD (sampled at mo 0, 1, 2, 3), as well as single plasma samples from a group of 30 healthy control participants. The levels of alpha-syn in plasma varied greatly between individuals, but were remarkably consistent over time within the same individual with PD. The mean level of phospho-alpha-syn was found to be higher (P=0.053) in the PD samples than the controls, whereas this was not the case for total alpha-syn (P=0.244), oligo-alpha-syn (P=0.221), or oligo-phospho-alpha-syn (P=0.181). Immunoblots of plasma revealed bands (at 21, 24, and 50-60 kDa) corresponding to phosphorylated alpha-syn. Thus, phosphorylated alpha-syn can be detected in blood plasma and shows more promise as a diagnostic marker than the nonphosphorylated protein. Longitudinal studies undertaken over a more extended time period will be required to determine whether alpha-syn can act as a marker of disease progression.-Foulds, P. G., Mitchell, J. D., Parker, A., Turner, R., Green, G., Diggle, P., Hasegawa, M., Taylor, M., Mann, D., Allsop, D. Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson's disease. FASEB J. 25, 4127-4137 (2011). www.fasebj.org