Towards biomarker-based diagnosis of Parkinson disease

The current clinical diagnostic criteria for Parkinson disease (PD) have limitations and are inherently insensitive to the earliest stages of disease, when classical motor signs can be absent. Imaging and genetic tests are currently used to support or establish a diagnosis of PD, but no validated biomarker-based diagnostic framework currently exists. Substantial progress has been made in the field of molecular disease markers, most notably with the development and validation of seed amplification assays (SAAs), which enable detection of very low levels of pathological α-synuclein in the cerebrospinal fluid and other biofluids and tissue. In this Review, we discuss the potential of α-synuclein SAAs and other biomarkers to improve diagnostic accuracy and enable earlier diagnosis of PD. We consider biological disease definitions that have been proposed on the basis of these biomarkers, highlighting their merits, limitations and implications for PD research and clinical management. Research is ongoing to determine the predictive value of PD biomarkers in healthy people and people with prodromal PD and to develop markers that are sensitive to disease progression, both of which are key for implementation of trials involving drugs designed to modify or prevent disease. Integrating clinical, genetic, molecular and imaging biomarkers should enable earlier, more accurate diagnosis of PD and characterization of PD subtypes, thereby enabling personalized treatment to slow or even prevent PD.