The two cut-offs approach for plasma p-tau217 in detecting Alzheimer's disease in subjective cognitive decline and mild cognitive impairment

BACKGROUND: The study aimed to explore the applicability of plasma phosphorylated tau (p-tau)217 in identifying patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) carrying Alzheimer's disease (AD) pathology in real-world settings. METHODS: Fifty SCD, 87 MCI, and 50 AD-demented patients underwent blood collection to dose plasma p-tau217 with a fully automated Lumipulse G600II assay. Patients were classified according to the Revised Criteria of the Alzheimer's Association Workgroup as Core1+ or Core1- (based on amyloid positron emission tomography, cerebrospinal fluid [CSF] amyloid beta [A beta]42/A beta 40, CSF p-tau181/A beta 42). RESULTS: Plasma p-tau217 was accurate for discriminating between Core1+ and Core1- patients (area under the curve = 0.92) with an optimal cut-off value of 0.274 pg/mL, revealing good accuracy (86.29%), positive predictive value (PPV; 88.18%), and negative predictive value (NPV; 83.09%). The two cut-offs approach (0.229-0.516 pg/mL) showed higher accuracy (91.11%), a PPV of 96.25% and a NPV of 83.63%. CONCLUSION: The two cut-offs approach provides for stronger accuracy, PPV, and NPV than a single cut-off, making reliable the clinical application of plasma p-tau217 for early detection of AD in real-world settings. Highlights Plasma phosphorylated tau (p-tau)217 was highly accurate in detecting Alzheimer's disease (AD) pathology. The two cut-offs approach increased plasma p-tau217 accuracy for AD diagnosis. Even when measured with immunoassay, p-tau217 is a good biomarker for AD diagnosis. Transition of p-tau217 from research setting to clinical practice seems feasible.