Plasma biomarkers for neurodegenerative disorders: ready for prime time?

Several plasma biomarkers for Alzheimer's disease and related disorders (ADRD) have demonstrated clinical and technical robustness. However, are they ready for clinical implementation? This review critically appraises current evidence for and against the immediate use of plasma biomarkers in clinical care. RECENT FINDINGS: Plasma biomarkers have significantly improved our understanding of ADRD time-course, risk factors, diagnosis and prognosis. These advances are accelerating the development and in-human testing of therapeutic candidates, and the selection of individuals with subtle biological evidence of disease who fit the criteria for early therapeutic targeting. However, standardized tests and well validated cut-off values are lacking. Moreover, some assays (e.g., plasma Aβ methods) have poor robustness to withstand inevitable day-to-day technical variations. Additionally, recent reports suggest that common comorbidities of aging (e.g., kidney disease, diabetes, hypertension) can erroneously affect plasma biomarker levels, clinical utility and generalizability. Furthermore, it is unclear if health disparities can explain reported racial/ethnic differences in biomarker levels and functions. Finally, current clinically approved plasma methods are more expensive than CSF assays, questioning their cost effectiveness. SUMMARY: Plasma biomarkers have biological and clinical capacity to detect ADRD. However, their widespread use requires issues around thresholds, comorbidities and diverse populations to be addressed.