The invention provides methods of detecting alpha-synuclein using a capture antibody and a reporter antibody. The capture antibody binds preferentially to full-length alpha- synuclein phosphorylated at residue 129 (PS129 alpha-synuclein) over unphosphorylated full- length alpha-synuclein. The 11A5 antibody is an example of a suitable capture antibody. The reporter antibody binds to an epitope within residues 40-55 of alpha-synuclein. The 23E8 antibody is an example of such an antibody. Because only a small proportion of alpha-synuclein is phosphorylated high sensitivity of detection below picomolar is advantageous.