Plasma tau biomarkers are distinctly associated with tau tangles and decreased with Lewy body pathology
The plasma phosphorylated tau (p-tau)217 ratio, followed by the p-tau205 ratio and p-tau217, were the best-performing biomarkers for detecting neuropathologically confirmed Alzheimer's disease (AD). In high AD cases, p-tau217 showed associations with neurofibrillary tangle (NFT) counts across all regions, while p-tau205 was primarily linked to the frontal cortex, and non-phosphorylated tau peptides were linked to the temporal cortex. We observed a decline in plasma tau levels as Lewy body pathology progressed, even among individuals at the same tau Braak stage. All plasma biomarkers correlated with creatinine levels, as a marker of renal dysfunction, but this effect was mitigated when using the ratios. Plasma p-tau199 displayed a distinct behavior compared to other p-tau species, showing no association with NFT counts in any brain region, but demonstrating significant correlations with brain volume and an effect on survival time.
Authors
- Elizabeth Valeriano-Lorenzo (ORCID: https://orcid.org/0000-0003-2294-2691)
- Gunnar Brinkmalm (ORCID: https://orcid.org/0000-0001-6958-2393)
- Juan Lantero‐Rodriguez (ORCID: https://orcid.org/0000-0002-7426-678X)
- Francisco Javier López‐González (ORCID: https://orcid.org/0000-0001-8990-0344)
- Alfredo Ramı́rez (ORCID: https://orcid.org/0000-0003-4991-763X)
- Iván Burgueño‐García (ORCID: https://orcid.org/0000-0003-2573-4644)
- María Ascensión Zea‐Sevilla (ORCID: https://orcid.org/0000-0002-6775-5411)
- Maria J. Lopez‐Martinez (ORCID: https://orcid.org/0000-0003-4009-6206)
- Laia Montoliu‐Gaya (ORCID: https://orcid.org/0000-0001-7684-6318)
- Pascual Sánchez‐Juan (ORCID: https://orcid.org/0000-0002-6081-8037)
- Belén Frades
- Kaj Blennow
- Henrik Zetterberg (ORCID: https://orcid.org/0000-0003-3930-4354)
- Meritxell Valentí (ORCID: https://orcid.org/0000-0002-2918-868X)
- Ana Belén Pastor (ORCID: https://orcid.org/0000-0001-9637-4688)
- Johan Gobom
- Nicholas J. Ashton
- Alicia Ruiz-González
- Teodoro del Ser (ORCID: https://orcid.org/0000-0001-9806-7083)
- Laura Saiz-Aúz (ORCID: https://orcid.org/0000-0001-9489-5455)
- Paloma Ruiz-Valderrey
Institutions
- Alzheimer's Association (US)
- Queen Mary University of London (GB)
- King's College London (GB)
- Hong Kong Science and Technology Parks Corporation (HK)
- Sahlgrenska University Hospital (SE)
- UK Dementia Research Institute (GB)
- NIHR Queen Square Dementia Biomedical Research Unit (GB)
- Banner Sun Health Research Institute (US)
- Fundacion Centro De Investigacion De Enfermedades Neurologicas (ES)
- Banner Alzheimer’s Institute
- University College London (GB)
- University of Gothenburg (SE)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1002/alz.70562
- Citations
- 1
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.16
Funders
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- BrightFocus Foundation
- Familjen Erling-Perssons Stiftelse
- Cure Alzheimer's Fund
- Gun och Bertil Stohnes Stiftelse
- Stiftelsen för Gamla Tjänarinnor
- EU Joint Programme – Neurodegenerative Disease Research
- University College London
- European Commission
- Hjärnfonden
- Vetenskapsrådet
- Alzheimerfonden
- UK Dementia Research Institute
- National Institutes of Health
- HORIZON EUROPE Framework Programme