Quantification of alpha-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies

The pursuit of laboratory tests that allow for the reliable and inexpensive identification of subjects with parkinsonism represents a hot topic in translational neuroscience. This unmet need affects the counseling of presymptomatic, at-risk subjects and delays the accurate diagnosis of already symptomatic individuals. The absence of validated markers that are closely linked to the pathological disease process also compromises the objective monitoring of therapeutic interventions in clinical trials. Typical Parkinson's disease represents a heterogenous syndrome (but the majority of patients suffer from neurodegeneration) that is linked to the misprocessing of alpha-synuclein (alpha-Syn). The identification of alpha-Syn as a bona fide constituent of human cerebrospinal fluid and its quantification in early cross-sectional studies represent the beginning of a new chapter in Parkinson's disease research. It will determine what role, if any, cerebrospinal fluid alpha-Syn plays as a biomarker candidate in Lewy inclusion-positive forms of parkinsonism. This article focuses on the progress that has been made in seven recently published papers and highlights the challenges that lie ahead. We also provide specific information regarding standardized operating procedures for cerebrospinal fluid collection in PD biomarker research efforts.