Plasma biomarkers as stand‐alone tests in the diagnosis of Alzheimer's disease.

Background: Several recent studies have provided evidence for high diagnostic performance of plasma biomarkers for AD, with Area Under the Curve values sometimes exceeding 90%. However, positive and negative predictive values are rarely reported yet are critical for interpreting individual‐level screening test results. Method: We determined positive and negative predictive values of plasma biomarkers (p‐tau181, p‐tau217, p‐tau231, GFAP and NfL) for biological AD (A+T+, determined either with PET or CSF) in the TRIAD, WRAP, ALFA+, BIODEGMAR, ADNI and McGill memory clinic cohorts (total n = 2219). We also determined positive and negative predictive values for specific clinical scenarios: MCI and mild AD – two populations that may benefit from disease‐modifying therapies in AD. Prevalence estimates of biological AD in these groups were taken from the Mayo Clinic Study of Aging. Result: P‐tau217 had the highest positive and negative predictive values of all biomarkers in all cohorts, with above 80% positive and negative predictive values. In individuals with MCI, an etiologically heterogeneous syndrome, plasma p‐tau217 had sufficiently high performance to rule out biological AD in differential diagnosis. In mild AD dementia, plasma p‐tau217 could rule in biological AD, but follow‐up with PET/CSF will likely be needed to confirm the absence of AD. Conclusion: Plasma biomarkers have the potential to be used as stand‐alone diagnostic tools in specific clinical scenarios. In MCI, a negative plasma p‐tau217 could rule out AD as a cause of cognitive impairment, but a positive result should be followed up with PET/CSF. In mild AD dementia, a positive plasma p‐tau217 result can rule in biological AD, but a negative result should be followed up with PET/CSF. [ABSTRACT FROM AUTHOR]