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

Abstract

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 α-synuclein in the pathophysiology of Parkinson's disease and hence major ongoing efforts to identify biomarkers for Parkinson's disease are aimed at measuring α-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, α-synuclein in cerebrospinal fluid as a diagnostic marker for Parkinson's disease is reviewed, including measures of total α-synuclein, oligomeric and phosphorylated α-synuclein, and seeding activity of α-synuclein.

Keywords: Aggregation; Biomarker; Cerebrospinal fluid; Oligomers; Parkinson's disease; Prion; Protein misfolding cyclic amplification assay; Real-time quaking-induced conversion; Seeding; α-Synuclein.