Quantification of α-synuclein in cerebrospinal fluid: how ideal is this biomarker for Parkinson's disease?

The quantification of α-synuclein (αSyn) in cerebrospinal fluid (CSF) has been proposed as a diagnostic biomarker for Parkinson's disease and other αSyn-related diseases, such as multiple system atrophy and dementia with Lewy bodies. Most studies show decreased levels of αSyn in diseased CSF samples compared to control samples, but discrepant findings and overlapping values have been a major limitation for the use of CSF αSyn as a biomarker. This review addresses the current knowledge and investigates whether CSF αSyn is an ideal biomarker that can detect fundamental neuropathology features. It will also discuss whether CSF αSyn has been validated in neuropathologically confirmed cases, whether it shows a diagnostic sensitivity and whether it has a specificity above 80%. The review of current literature will also determine if sampling CSF αSyn is reliable, reproducible, noninvasive, simple to perform, inexpensive, and whether it has been investigated by at least two independent studies. CSF αSyn appears to meet most of these criteria, which have been proposed for ideal biomarkers, but further validation of this and other markers is needed to best introduce a panel of biomarkers in the early and differential diagnosis of Parkinson's disease.