LAUSR

A critical need exists to develop biomarkers for Parkinson’s disease (PD). Facilitating the evolution toward personalized medicine, validated biomarkers hold the promise of improved diagnostic accuracy, disease monitoring, patient stratification, and objectively measuring treatment responses. The lack of biomarkers for PD has limited the clinical translation of promising preclinical disease-modifying therapies. Indeed, sole reliance on clinical assessments and rating scales as outcome measures may have contributed to the recent failure of isradipine and inosine phase 3 studies. Such measures are frequently confounded by symptomatic treatment and unable to reflect subtle but important changes in the disease state that may reflect modification of disease progression. Moreover, given the welldescribed clinical heterogeneity of PD, another goal of biomarkers centers on the stratification and enrichment of patient populations recruited into clinical trials. Testing well-defined disease subgroups, in place of the traditional large and heterogenous patient cohorts, could improve clinical trial efficacy. Furthermore, the identification and subsequent enrollment of asymptomatic individuals at risk for PD into neuroprotective drug trials remains an important goal for biomarker development. The PD biofluid biomarker discovery field, previously fraught with disappointing and inconsistent results, has recently gathered significant momentum. Guidelines aiming to generate robust biomarkers recommend a shift toward longitudinal, large-scale collaborative studies and standardization of methods employed. Furthermore, emerging promising biomarkers should subsequently be subjected to an extensive validation process. Clinically useful biomarkers must fulfill the following criteria, listed as: a reasonable effect size (ie, area under the curve, AUC > 0.8); reproducibility with minimal overlap in values between disease and control subjects; easily quantifiable and unaffected by other comorbidities. Driven by technological advances and ease of sample accessibility, identifying biofluid-based biomarkers in PD (particularly, in blood and cerebrospinal fuid [CSF]) has overtaken traditional neuroimaging as a research focal point. Although no such biomarkers meet the aforementioned criteria for clinical utility, this Viewpoint will summarize promising findings in the search for biofluid biomarkers in PD, highlighting key challenges and setting out recommendations for future directions.