Plasma p-tau217 and neurofilament/p-tau217 ratio in differentiating Alzheimer's disease from syndromes associated with frontotemporal lobar degeneration

Introduction: Plasma-based biomarkers have shown promise for clinical implementation, but their accuracy in differentiating Alzheimer's disease (AD) from syndromes associated with frontotemporal lobar degeneration (FTLD) has yet to be fully investigated. This study assessed the potential of plasma biomarkers for differential diagnosis. Methods: This cohort study included 374 participants (96 AD, 278 FTLD). Plasma phosphorylated tau (p-tau)217, neurofilament light chain (NfL), brain-derived tau, glial fibrillary acidic protein, and the amyloid beta1-42/1-40 ratio were measured. Receiver operating characteristic curve analyses assessed diagnostic accuracy, and a three-range threshold approach was used to stratify patients based on the most accurate biomarker. Results: Plasma p-tau217 effectively distinguished AD from FTLD, with the NfL/p-tau217 ratio showing superior accuracy. The three-range approach identified thresholds with 95% and 97.5% sensitivity and specificity, reducing the need for cerebrospinal fluid testing by 75% and 54%, respectively. Discussion: Plasma p-tau217 and the NfL/p-tau217 ratio are promising non-invasive biomarkers for differentiating AD from FTLD, suggesting their use as a potential alternative to traditional diagnostic methods. Highlights: Plasma phosphorylated tau (p-tau)217 distinguishes Alzheimer's disease (AD) from frontotemporal lobar degeneration (FTLD) with high accuracy. The neurofilament light chain/p-tau217 ratio showed the highest accuracy for differentiating AD from FTLD. A three-range threshold reduces the need for invasive cerebrospinal fluid testing or amyloid positron emission tomography imaging.