Diagnostic utility of plasma ptau217, ptau181, GFAP for Alzheimer disease in a heterogeneous younger onset dementia clinical cohort

ABSTRACT Objective We investigated diagnostic utility of phosphorylated tau 217 and 181 (ptau217, ptau181), glial fibrillary acidic protein (GFAP), amyloid beta 42 and 40 (Aβ42, Aβ40), neurofilament light (NfL) to distinguish AD from non-AD conditions, in a heterogenous clinical cohort of younger people. Methods Plasma biomarkers were analysed using ultrasensitive technology, and compared in patients with CSF Alzheimer disease profiles (A+T+) to other profiles (OtherAT). Results Seventy-nine patients were included, median age 60.8 years: 16 A+T+, 63 OtherAT. Ptau217, ptau181, GFAP were significantly elevated in A+T+ compared to OtherAT (3.67 vs 1.12pg/mL, 3.87 vs 1.79pg/mL, 189 vs 80pg/mL, respectively). ptau217 distinguished AD from OtherAT with 90% accuracy (88% specificity, 100% sensitivity) Conclusions Plasma ptau217 has strong diagnostic utility to diagnose AD in a clinically relevant, younger cohort of people with symptoms, adding further weight for a simple diagnostic blood test for AD as a cause of a patient’s symptoms.