Plasma p-tau217, NfL, GFAP diagnostic performance and biomarker profiles in Alzheimer&#39;s disease, frontotemporal dementia, and psychiatric disorders, in a prospective unselected neuropsychiatry memory clinic

Eratne, D; Kang, M; Malpas, CB; Dang, C; Lewis, C; Bhalala, OG; Li, QX; Collins, S; Masters, CL; Loi, SM; Santillo, AF; Blennow, K; Zetterberg, H; Velakoulis, D

Plasma p-tau217, NfL, GFAP diagnostic performance and biomarker profiles in Alzheimer's disease, frontotemporal dementia, and psychiatric disorders, in a prospective unselected neuropsychiatry memory clinic

Author(s): Eratne, D; Kang, M; Malpas, CB; Dang, C; Lewis, C; Bhalala, OG; Li, QX; Collins, S; Masters, CL; Loi, SM; Santillo, AF; Blennow, K; Zetterberg, H; Velakoulis, D;
Details: Publication Year 2025-10,Volume 21,Issue #10,Page e70717
Journal Title: Alzheimer’s & Dimentia
Abstract: INTRODUCTION: Plasma biomarkers offer promise for improving the diagnosis of Alzheimer's disease (AD) and differentiating AD and other neurodegenerative disorders (NDs) like frontotemporal dementia (FTD) from primary psychiatric disorders (PPDs), particularly in younger patients. METHODS: In this prospective study, we investigated plasma phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in 341 unselected participants from a neuropsychiatry memory clinic, including AD (n = 40), behavioral variant FTD (bvFTD) (n = 15), PPD (n = 69), other NDs, and controls. RESULTS: Plasma p-tau217 showed strong diagnostic performance for distinguishing AD from bvFTD (96% accuracy) and PPD (93% accuracy). NfL best distinguished all NDs from PPD, while GFAP did not bring additional value. Biomarker profiles using predefined cut-offs and age-adjusted z-scores further clarified group differences. DISCUSSION: Plasma p-tau217 and NfL have strong diagnostic utility in real-world, diagnostically complex cohorts. These findings support implementation of scalable blood-based biomarkers to improve early and accurate diagnosis in memory clinical settings. HIGHLIGHTS: Plasma p-tau217 was significantly elevated in AD compared to other disorders. P-tau217 distinguished AD from bvFTD with high accuracy. P-tau217 distinguished AD from PPDs with high accuracy. NfL/p-tau217 ratio and GFAP added limited diagnostic value compared to p-tau217 and NfL. Findings support blood biomarkers in younger, real-world clinical cohorts.
Publisher: Wiley
Keywords: Humans; *Alzheimer Disease/blood/diagnosis; *tau Proteins/blood; Female; Male; Biomarkers/blood; *Frontotemporal Dementia/blood/diagnosis; *Glial Fibrillary Acidic Protein/blood; *Neurofilament Proteins/blood; Aged; Prospective Studies; Middle Aged; *Mental Disorders/blood/diagnosis; Aged, 80 and over; Alzheimer's disease; Gfap; age‐adjusted reference ranges; blood‐based biomarkers; diagnostic accuracy; frontotemporal dementia; memory clinic; neurodegeneration; neurofilament light chain; plasma biomarkers; primary psychiatric disorders; prospective cohort; psychiatric misdiagnosis; p‐tau217
Research Division(s): Genetics and Gene Regulation
PubMed ID: 41025379
Publisher's Version: https://doi.org/10.1002/alz.70717
Open Access at Publisher's Site: https://doi.org/10.1002/alz.70717
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-10-20 01:57:43

Last Modified: 2025-10-20 01:57:58