Clinical Validation of Novel Immunoassays for Plasma Phosphorylated Tau 217, 212, 181, 231, and Brain‐Derived Tau Across the Biochemical Spectrum of Alzheimer's Disease
Plasma biomarkers have emerged as promising less invasive alternatives for Alzheimer's disease (AD) detection. However, the diagnostic performance of phosphorylated tau (p-tau) isoforms remains incompletely validated. In a cohort of 160 patients from a memory clinic, plasma levels of p-tau217, p-tau212, p-tau181, p-tau231, and BD-tau were measured using Single Molecule Array (Simoa) in-house assays, alongside NFL and GFAP. Subjects were classified using the Erlangen Score into Controls (n = 53), neurochemically possible AD (n = 27), and probable AD (n = 80). Plasma concentrations of all p-tau isoforms were significantly elevated in both Possible AD and Probable AD groups compared to Controls (p < 0.001). Notably, p-tau217 exhibited the highest diagnostic accuracy (AUC = 0.954) and correlated with CSF classical biomarkers. A positive result for p-tau217 increases the probability of AD almost fivefold. Plasma p-tau217 reflects AD neurochemical changes and has high negative predictive value, supporting its use as a screening tool. However, moderate PPV suggests the need for confirmatory testing to ensure an accurate diagnosis.
Authors
- Manuel Maler
- Agnieszka Kulczyńska‐Przybik (ORCID: https://orcid.org/0000-0002-9889-3585)
- Jörg Hanrieder (ORCID: https://orcid.org/0000-0001-6059-198X)
- Michael Turton
- Kaj Blennow (ORCID: https://orcid.org/0000-0002-1890-4193)
- Przemysław Radosław Kac (ORCID: https://orcid.org/0000-0001-5083-0924)
- Piotr Lewczuk (ORCID: https://orcid.org/0000-0002-8101-6535)
- Thomas K. Karikari (ORCID: https://orcid.org/0000-0003-1422-4358)
- Fernando C. Ortíz (ORCID: https://orcid.org/0000-0002-4776-4492)
- Barbara Mroczko (ORCID: https://orcid.org/0000-0002-4075-8479)
- Maciej Dulewicz (ORCID: https://orcid.org/0000-0002-7149-017X)
- Henrik Zetterberg (ORCID: https://orcid.org/0000-0003-3930-4354)
- Timo Jan Oberstein
- Johannes Kornhuber
- Peter Harrison
Institutions
- University of Science and Technology of China (CN)
- University of Wisconsin–Madison (US)
- Medical University of Białystok (PL)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Science for Life Laboratory (SE)
- Sahlgrenska University Hospital (SE)
- Sorbonne Université (FR)
- Universitätsklinikum Erlangen (DE)
- Pitié-Salpêtrière Hospital (FR)
- UK Dementia Research Institute (GB)
- Biocompatibles (United Kingdom) (GB)
- Institut du Cerveau (FR)
- University College London (GB)
- University of Gothenburg (SE)
Publication Details
- Journal
- Journal of Neurochemistry
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1111/jnc.70313
- Citations
- 1
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Alzheimer's Drug Discovery Foundation
- Familjen Erling-Perssons Stiftelse
- Stiftelsen för Gamla Tjänarinnor
- National Institute for Health and Care Research
- University College London
- European Commission
- Hjärnfonden
- Vetenskapsrådet
- Magnus Bergvalls Stiftelse
- UK Dementia Research Institute
- Fondation pour la Recherche sur Alzheimer
- National Institutes of Health