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.
Dhamidhu Eratne, Matthew Kang, Charles B Malpas, Christa Dang, Courtney Lewis, Oneil G Bhalala, Qiao-Xin Li, Steven Collins, Colin L Masters, Samantha M Loi, Alexander F Santillo, Kaj Blennow, Henrik Zetterberg, Dennis Velakoulis
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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.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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