Disclosure of plasma p-tau217 measure improves diagnostic confidence in patients with Alzheimer's disease versus syndromes associated with frontotemporal lobar degeneration

Valentina Cantoni¹, Maria Sofia Cotelli², Matteo Rota³, Antonella Alberici², Ilenia Libri², Hanna Huber^{4

5}, Kübra Tan⁴, Roberta Ghidoni⁶, Sonia Bellini⁶, Henrik Zetterberg^{4

7

8

9

10

11}, Kaj Blennow^{4

7

12

13}, Nicholas J Ashton^{4

14

15}, Barbara Borroni^{1

6}

Affiliations

¹ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
² Department of Continuity of Care and Frailty, ASST Spedali Civili, Brescia, Italy.
³ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁵ German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
⁶ Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
⁷ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁹ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁰ UK Dementia Research Institute at UCL, London, UK.
¹¹ Hong Kong Center for Neurodegenerative Diseases, Shatin, Hong Kong, China.
¹² Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
¹³ 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.
¹⁴ Banner Sun Health Research Institute, Sun City, Arizona, USA.
¹⁵ Banner Alzheimer's Institute and University of Arizona, Phoenix, Arizona, USA.

PMID: 40371667
PMCID: PMC12079395
DOI: 10.1002/alz.70289

Comparative Study

Disclosure of plasma p-tau217 measure improves diagnostic confidence in patients with Alzheimer's disease versus syndromes associated with frontotemporal lobar degeneration

Valentina Cantoni et al. Alzheimers Dement. 2025 May.

. 2025 May;21(5):e70289.

doi: 10.1002/alz.70289.

Authors

Affiliations

¹ Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
² Department of Continuity of Care and Frailty, ASST Spedali Civili, Brescia, Italy.
³ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁴ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
⁵ German Center of Neurodegenerative Diseases (DZNE), Bonn, Germany.
⁶ Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio, Fatebenefratelli, Brescia, Italy.
⁷ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁸ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁹ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹⁰ UK Dementia Research Institute at UCL, London, UK.
¹¹ Hong Kong Center for Neurodegenerative Diseases, Shatin, Hong Kong, China.
¹² Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
¹³ 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.
¹⁴ Banner Sun Health Research Institute, Sun City, Arizona, USA.
¹⁵ Banner Alzheimer's Institute and University of Arizona, Phoenix, Arizona, USA.

PMID: 40371667
PMCID: PMC12079395
DOI: 10.1002/alz.70289

Abstract

Introduction: Further research is needed to understand the performance of plasma phosphorylated tau (p-tau)217 in the diagnostic thinking at the individual patient level. We evaluated the incremental diagnostic value of plasma p-tau217, expressed in terms of diagnostic confidence of Alzheimer's disease (DCAD; range 0-100).

Methods: Two hundred thirty-two patients with dementia were included and scored in terms of DCAD in a three-step consecutive assessment: (1) clinical work-up, (2) clinical work-up plus plasma p-tau217, and (3) clinical work-up, plasma p-tau217, plus conventional amyloid markers. Two blinded neurologists were asked to review DCAD at each step.

Results: DCAD accuracy, expressed as area under the curve, significantly increased from 0.93 with clinical work-up alone, to 0.97 with clinical work-up plus plasma p-tau217 (P = 0.01), with no further increase with the addition of conventional amyloid markers (0.99, P = 0.13).

Discussion: Plasma p-tau217 in addition to routine assessment significantly enhances diagnostic confidence that is comparable to well-established amyloidosis biomarkers.

Highlights: Plasma phosphorylated tau (p-tau)217 measurements increase diagnostic confidence of Alzheimer's disease. Plasma p-tau217 increases diagnostic confidence comparable to traditional markers. Plasma p-tau217 dosage may be helpful in addition to routine assessment.

Keywords: Alzheimer's disease; blood‐based biomarkers; diagnostic confidence; frontotemporal lobar degeneration; plasma phosphorylated tau217.

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Conflict of interest statement

H.Z. has served on scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). K.B. has served as a consultant and on advisory boards for Abbvie, AC Immune, ALZPath, AriBio, Beckman–Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sanofi, and Siemens Healthineers; has served on data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials, and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai, and Roche Diagnostics; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. B.B. has served on scientific advisory boards for Alector, Alexion/Astrazeneca, AviadoBio, Lilly, Denali, Wave, and UCB. The other authors report nothing to disclose. Author disclosures are available in supporting information.

Figures

**FIGURE 1**
ROC curves of DCAD for clinical work‐up, clinical work‐up plus plasma p‐tau217, and clinical work‐up and p‐tau217 plus amyloid markers in differentiating AD from FTLD (A), AD from bvFTD (B), and AD from PPA (C). AD, Alzheimer's disease; AUC, area under the curve; bvFTD, behavioral variant frontotemporal dementia; clinical w‐up, clinical work‐up; DCAD, diagnostic confidence of Alzheimer's disease; FTLD, frontotemporal lobar degeneration; PPA, primary progressive aphasia; p‐tau, phosphorylated tau; ROC, receiver operating characteristic

See this image and copyright information in PMC

References

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Disclosure of plasma p-tau217 measure improves diagnostic confidence in patients with Alzheimer's disease versus syndromes associated with frontotemporal lobar degeneration

Affiliations

Disclosure of plasma p-tau217 measure improves diagnostic confidence in patients with Alzheimer's disease versus syndromes associated with frontotemporal lobar degeneration

Authors

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Abstract

Conflict of interest statement

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