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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

Eratne, Dhamidhu ; Kang, Matthew ; Malpas, Charles B. ; Dang, Christa ; Lewis, Courtney ; Bhalala, Oneil G. ; Li, Qiao Xin ; Collins, Steven ; Masters, Colin L. and Loi, Samantha M. , et al. (2025) In Alzheimer's & dementia : the journal of the Alzheimer's Association 21(10).
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%... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
age‐adjusted reference ranges, Alzheimer's disease, blood‐based biomarkers, diagnostic accuracy, frontotemporal dementia, GFAP, memory clinic, neurodegeneration, neurofilament light chain, plasma biomarkers, primary psychiatric disorders, prospective cohort, psychiatric misdiagnosis, p‐tau217
in
Alzheimer's & dementia : the journal of the Alzheimer's Association
volume
21
issue
10
article number
e70717
publisher
Wiley
external identifiers
  • scopus:105017567730
  • pmid:41025379
ISSN
1552-5279
DOI
10.1002/alz.70717
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
id
23141df2-58d7-4635-95f0-c635baf497f4
date added to LUP
2025-10-14 07:25:39
date last changed
2025-11-25 11:27:36
@article{23141df2-58d7-4635-95f0-c635baf497f4,
  abstract     = {{<p>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.</p>}},
  author       = {{Eratne, Dhamidhu and Kang, Matthew and Malpas, Charles B. and Dang, Christa and Lewis, Courtney and Bhalala, Oneil G. and Li, Qiao Xin and Collins, Steven and Masters, Colin L. and Loi, Samantha M. and Santillo, Alexander F. and Blennow, Kaj and Zetterberg, Henrik and Velakoulis, Dennis}},
  issn         = {{1552-5279}},
  keywords     = {{age‐adjusted reference ranges; Alzheimer's disease; blood‐based biomarkers; diagnostic accuracy; frontotemporal dementia; GFAP; memory clinic; neurodegeneration; neurofilament light chain; plasma biomarkers; primary psychiatric disorders; prospective cohort; psychiatric misdiagnosis; p‐tau217}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{10}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's & dementia : the journal of the Alzheimer's Association}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1002/alz.70717}},
  doi          = {{10.1002/alz.70717}},
  volume       = {{21}},
  year         = {{2025}},
}