Disclosed is amethod of diagnosing an elevated level of a-synuclein in the brain of a human subject, said method comprising: (a) assaying a level of a-synuclein in a blood plasma sample or cerebrospinal fluid (CSF) sample obtained from the human subject at a specified time interval following peripheral administration to the human subject of an anti-a-synuclein antibody or antigen-binding fragment thereof, wherein the antibody or fragment thereof can bind a-synuclein with sufficient affinity to alter a net efflux of a-synuclein from brain to blood or CSF; and (b) comparing the level of the a-synuclein in the blood plasma sample or CSF sample assayed to a reference standard, wherein a difference or similarity between the level of a-synuclein in the blood plasma sample or CSF sample and the reference standard correlates with the level of a-synuclein in the brain of the human subject.