Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease

Joyce R Chong; Saima Hilal; Boon Yeow Tan; Narayanaswamy Venketasubramanian; Michael Schöll; Henrik Zetterberg; Kaj Blennow; Nicholas J Ashton; Christopher P Chen; Mitchell K P Lai

doi:10.1002/alz.14502

Clinical utility of plasma p-tau217 in identifying abnormal brain amyloid burden in an Asian cohort with high prevalence of concomitant cerebrovascular disease

Alzheimers Dement. 2025 Jan 14:e14502. doi: 10.1002/alz.14502. Online ahead of print.

Authors

Joyce R Chong^{1

2}, Saima Hilal^{1

2

3}, Boon Yeow Tan⁴, Narayanaswamy Venketasubramanian⁵, Michael Schöll^{6

7

8}, Henrik Zetterberg^{6

7

9

10

11

12}, Kaj Blennow^{6

9

13

14}, Nicholas J Ashton^{6

15}, Christopher P Chen^{1

2}, Mitchell K P Lai^{1

2}

Affiliations

¹ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
² Memory, Aging and Cognition Centre, National University Health Systems, Singapore, Singapore.
³ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
⁴ St Luke's Hospital, Singapore, Singapore.
⁵ Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore.
⁶ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
⁷ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
⁸ Department of Neuropsychiatry, Sahlgrenska University Hospital, Göteborg, Sweden.
⁹ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden.
¹⁰ UK Dementia Research Institute at UCL, London, UK.
¹¹ Hong Kong Center for Neurodegenerative Diseases, Hong Kong, P.R. China.
¹² Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
¹³ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
¹⁴ 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.
¹⁵ Banner Sun Health Research Institute, Sun City, Arizona, USA.

PMID: 39807654
DOI: 10.1002/alz.14502

Abstract

Introduction: Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance of a plasma immunoassay for tau phosphorylated at threonine 217 (p-tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based on a three-range reference, which stratified patients into low-, intermediate-, and high-risk groups for Aβ+.

Methods: Brain amyloid status (Aβ- [n = 142] vs Aβ+ [n = 73]) on amyloid PET scans was assessed along with the plasma ALZpath p-tau217 assay to derive three-range reference points for PET Aβ+ based on 90% sensitivity (lower threshold) and 90% specificity (upper threshold).

Results: Plasma p-tau217 (area under the curve [AUC] = 0.923) outperformed routine clinical assessments (AUC = 0.760-0.819; p ≤ 0.003) and other plasma biomarkers (AUC = 0.817-0.834; p < 0.001). The high-risk group showed significantly higher rates of cognitive decline than the low-risk group.

Discussion: Risk stratification for PET Aβ+ based on a plasma p-tau217 assay demonstrated potential diagnostic and prognostic utility in an Asian cohort with concomitant CeVD.

Highlights: The utility of plasma p-tau217 to detect brain amyloid beta pathology (Aβ+) was studied in an Asian cohort with concomitant cerebrovascular disease Plasma tau phosphorylated at threonine 217 (p-tau217) showed superior utility in detecting Aβ+ compared to neuroimaging measures, clinical workup, or other blood biomarkers including p-tau181, glial fibrillary protein (GFAP), and Aβ Higher plasma p-tau217 correlated with faster cognitive decline Plasma p-tau217 shows promise as an Alzheimer's disease (AD) diagnostic and prognostic biomarker in diverse populations.

Keywords: Alzheimer's disease; amyloid; biomarkers; cognitive impairment; diagnosis; prognosis.

Abstract

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