Diagnostic biomarkers for Parkinson's disease: focus on a-synuclein in cerebrospinal fluid

Diagnostic biomarkers are measures that detect or confirm the presence of a disease or identify individuals with a subtype of the disease. For Parkinson's disease, unlike other neurodegenerative diseases such as Alzheimer's disease and Creutzfeldt-Jakob disease, diagnostic biomarkers remain elusive as none are yet available or approved for clinical use. A biomarker to diagnose early or prodromal Parkinson's disease with high accuracy would significantly enhance clinical practice as well as advance clinical therapeutic trials. Multiple lines of evidence support a role of a-synuclein in the pathophysiology of Parkinson's disease and hence major ongoing efforts to identify biomarkers for Parkinson's disease are aimed at measuring alpha-synuclein in peripheral tissues and biofluids, including cerebrospinal fluid. This work is still in the early stages of biomarker development and has been accompanied by both losses and victories. Here, alpha-synuclein in cerebrospinal fluid as a diagnostic marker for Parkinson's disease is reviewed, including measures of total alpha-synuclein, oligomeric and phosphorylated alpha-synuclein, and seeding activity of alpha-synuclein.