Performance of plasma p-tau217 and NfL in an unselected memory clinic setting.

Introduction: Plasma phosphorylated tau-217 (p-tau217) and neurofilament light (NfL) can differentiate between different dementias in selected cohorts. We aim to test the discrimination potential of these markers in a real-world cohort.

Methods: We measured p-tau217 (ALZpath) and NfL (Quanterix) in 415 (unselected) consecutive memory clinic patients. Biomarker levels were dichotomized as low/high to create four biomarker profiles based on p-tau217 and NfL levels.

Results: p-Tau217 levels were highest in patients with Alzheimer's disease (AD) dementia, whereas NfL levels were highest in patients with frontotemporal dementia (FTD). Low p-tau217/low NfL was associated mostly with non-neurological diagnoses (79%), and high p-tau217/low NfL indicated AD pathology at any stage (84%). Low p-tau217/high NfL indicated FTD (38%) and high p-tau217/high NfL indicated AD dementia (87%).

Discussion: p-Tau217 can identify AD pathology at any disease stage. NfL can differentiate FTD from other diagnoses (e.g., AD dementia). Plasma p-tau217 and NfL can support clinical decision-making, and we suggest using them as complements to standard clinical assessment.

Highlights: Phosphorylated tau-2017 (p-tau217) can detect Alzheimer's disease (AD) across the clinical continuum.Neurofilament light (NfL) can differentiate frontotemporal dementia (FTD) from other diagnoses (AD dementia, dementia with Lewy bodies [DLB], and Psychiatry).p-Tau217 may detect AD co-pathology in other diseases or dementia types (e.g., DLB).p-Tau217 and NfL show potential for clinical implementation.