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

Alberto Benussi; Hanna Huber; Kübra Tan; Valentina Cantoni; Jasmine Rivolta; Maria Sofia Cotelli; Andrea L Benedet; Kaj Blennow; Henrik Zetterberg; Nicholas J Ashton; Barbara Borroni

doi:10.1002/alz.14482

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

Alzheimers Dement. 2025 Jan 8. doi: 10.1002/alz.14482. Online ahead of print.

Authors

Alberto Benussi¹, Hanna Huber², Kübra Tan², Valentina Cantoni³, Jasmine Rivolta³, Maria Sofia Cotelli³, Andrea L Benedet², Kaj Blennow^{2

4

5

6}, Henrik Zetterberg^{2

7

8

9

10}, Nicholas J Ashton^{2

11

12}, Barbara Borroni^{13

14}

Affiliations

¹ Neurology Unit, Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska, Academy, University of Gothenburg, Gothenburg, Sweden.
³ Cognitive and Behavioural Neurology Unit, Department of Continuity of Care and Frailty, ASST Spedali Civili di Brescia, Brescia, Italy.
⁴ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
⁵ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
⁶ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, P.R. China.
⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁸ UK Dementia Research Institute, Department of Molecular Neuroscience, UCL, London, UK.
⁹ Hong Kong Center for Neurodegenerative Diseases, Division of Life Science, Clear Water Bay, Hong Kong, China.
¹⁰ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹¹ Banner Sun Health Research Institute, Sun City, Arizona, USA.
¹² Banner Alzheimer's Institute, Phoenix, Arizona, USA.
¹³ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
¹⁴ Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.

PMID: 39776166
DOI: 10.1002/alz.14482

Abstract

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 beta_1-42/_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.

Keywords: Alzheimer's disease; blood‐based biomarkers; diagnostic accuracy; frontotemporal lobar degeneration; neurofilament light chain; phosphorylated tau217.

Abstract

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