Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology

Plasma phosphorylated-tau (p-tau) biomarkers show high performance as first-in-line tests in the evaluation of patients with cognitive symptoms and have also found utility in clinical trials for anti-amyloid drug therapies for Alzheimer's disease (AD). Plasma p-tau212 is a novel blood biomarker that can discriminate cognitively unimpaired (CU) and subjective cognitive decline patients from mild cognitive impairment (MCI)-AD and AD dementia patients in clinical cohorts. Using Simoa technology, we evaluated plasma p-tau212 for its ability to detect emerging amyloid-beta (Aβ) pathology in CU individuals with brain amyloidosis from CSF Aβ42/40 ratio (n = 317) or Aβ PET scans (n = 277). We benchmarked plasma p-tau212 against p-tau181, p-tau217, and p-tau231 by comparing their accuracies and fold changes for detecting brain amyloidosis. Our results showed that all the plasma p-tau biomarkers are increased in the CU CSF Aβ + participants, with the highest median fold change observed for plasma p-tau212. Discrimination performance of the biomarkers to differentiate amyloid PET-positive from amyloid PET-negative participants differed between plasma p-tau biomarkers, being higher for plasma p-tau217 and p-tau212 compared to plasma p-tau181 and p-tau231. Furthermore, plasma p-tau212 was elevated in participants with low Aβ burden (CSF Aβ-positive, amyloid PET-negative), supporting its potential as a cost-effective, easily implemented biomarker for trial recruitment in early stages. Its further increase in Aβ PET-positive participants suggests additional utility for monitoring anti-amyloid therapies.

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Publication Details

Journal
Journal of Neurology
Published
2025-12-25
DOI
https://doi.org/10.1007/s00415-025-13572-5
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology

Kaj Blennow, Marc Suárez‐Calvet, Michael K Turton, Peter Harrison et al.
Journal of Neurology
Dementia and Cognitive Impairment Research
article

Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology

Kaj Blennow, Marc Suárez‐Calvet, Michael K Turton, Peter Harrison, Juan Domingo Gispert, Thomas K. Karikari, Armand González-Escalante, Przemysław R. Kac, Paula Ortiz-Romero, Mahnaz Shekari, Marta Milà-Alomà, Nicholas J. Ashton, Henrik Zetterberg
article en

Abstract

Plasma phosphorylated-tau (p-tau) biomarkers show high performance as first-in-line tests in the evaluation of patients with cognitive symptoms and have also found utility in clinical trials for anti-amyloid drug therapies for Alzheimer's disease (AD). Plasma p-tau212 is a novel blood biomarker that can discriminate cognitively unimpaired (CU) and subjective cognitive decline patients from mild cognitive impairment (MCI)-AD and AD dementia patients in clinical cohorts. Using Simoa technology, we evaluated plasma p-tau212 for its ability to detect emerging amyloid-beta (Aβ) pathology in CU individuals with brain amyloidosis from CSF Aβ42/40 ratio (n = 317) or Aβ PET scans (n = 277). We benchmarked plasma p-tau212 against p-tau181, p-tau217, and p-tau231 by comparing their accuracies and fold changes for detecting brain amyloidosis. Our results showed that all the plasma p-tau biomarkers are increased in the CU CSF Aβ + participants, with the highest median fold change observed for plasma p-tau212. Discrimination performance of the biomarkers to differentiate amyloid PET-positive from amyloid PET-negative participants differed between plasma p-tau biomarkers, being higher for plasma p-tau217 and p-tau212 compared to plasma p-tau181 and p-tau231. Furthermore, plasma p-tau212 was elevated in participants with low Aβ burden (CSF Aβ-positive, amyloid PET-negative), supporting its potential as a cost-effective, easily implemented biomarker for trial recruitment in early stages. Its further increase in Aβ PET-positive participants suggests additional utility for monitoring anti-amyloid therapies.

Journal of NeurologyVol. 273(1)
University of Wisconsin–Madison (US), University of Arizona (US), University of Pittsburgh (US), Universitat Pompeu Fabra (ES), South London and Maudsley NHS Foundation Trust (GB), Stavanger University Hospital (NO), Sahlgrenska University Hospital (SE), Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES), Pasqual Maragall Foundation (ES), Institute for Neurodegenerative Disorders (US), UK Dementia Research Institute (GB), Barcelonaβeta Brain Research Center (ES), Hospital Del Mar (ES), Biocompatibles (United Kingdom) (GB), National Hospital for Neurology and Neurosurgery (GB), Northern California Institute for Research and Education (US), University College London (GB), Indian Institute of Science Bangalore (IN), University of Gothenburg (SE)
Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Demensförbundet, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, National Institute for Health and Care Research, University College London, European Commission, Generalitat de Catalunya, Hjärnfonden, Vetenskapsrådet, UK Dementia Research Institute, Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona, National Institutes of Health, HORIZON EUROPE Framework Programme, Instituto de Salud Carlos III
Reduced inequalities
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