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Plasma tau biomarkers are distinctly associated with tau tangles and decreased with Lewy body pathology
Montoliu-Gaya L, Valeriano-Lorenzo E, Ashton NJ, López-González FJ, Lantero-Rodriguez J, Ruiz-González A, Pastor AB, Frades B et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-08-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
Introduction Plasma-to-autopsy studies are essential to understand how tau blood biomarkers change in relation to Alzheimer's disease (AD) brain pathology and how they are influenced by brain co-pathologies and comorbidities. Methods Plasma samples from 102 brain donors of the Vallecas Alzheimer Reina Sofia cohort were analyzed using a mass spectrometry method to measure the levels of six phosphorylated and two non-phosphorylated tau biomarkers. Results In cases with high pathological burden of AD, phosphorylated tau (p-tau)217 showed associations with neurofibrillary tangle counts across all regions, while p-tau205 was primarily linked to the frontal cortex, and the non-phosphorylated tau peptides were linked to the temporal cortex. Plasma tau levels decreased 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 phospho/non-phospho. Discussion Understanding how plasma tau biomarkers are influenced by co-pathologies and comorbidities is crucial for their accurate implementation. Highlights 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.
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APA 7th
Montoliu-Gaya, L., Valeriano-Lorenzo, E., Ashton, N. J., López-González, F. J., Lantero-Rodriguez, J., Ruiz-González, A., et al. (2025). Plasma tau biomarkers are distinctly associated with tau tangles and decreased with Lewy body pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70562
Vancouver
Montoliu-Gaya L, Valeriano-Lorenzo E, Ashton NJ, López-González FJ, Lantero-Rodriguez J, Ruiz-González A, et al. Plasma tau biomarkers are distinctly associated with tau tangles and decreased with Lewy body pathology. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70562. PMID: 40791093.
BibTeX
@article{montoliugaya2025-40791093,
author = {Montoliu-Gaya, L. and Valeriano-Lorenzo, E. and Ashton, N. J. and López-González, F. J. and Lantero-Rodriguez, J. and Ruiz-González, A. and Pastor, A. B. and Frades, B. and others},
title = {{Plasma tau biomarkers are distinctly associated with tau tangles and decreased with Lewy body pathology}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70562},
pmid = {40791093},
url = {https://doi.org/10.1002/alz.70562}
}
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Key findings
- Results In cases with high pathological burden of AD, phosphorylated tau (p-tau)217 showed associations with neurofibrillary tangle counts across all regions, while p-tau205 was primarily linked to the frontal cortex, and the 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.
- 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.
Why it matters
In 102 brain donors, plasma p-tau217 was associated with neurofibrillary tangles, and plasma tau levels decreased as Lewy body pathology progressed. This is a postmortem correlation study and does not test any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthModerate
Limitations
This was a brain-donor (autopsy) cohort of 102 people, so the findings describe correlations between blood and brain tissue after death and have not been shown to predict this regional pattern in living patients.
How this study scored 46/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 8 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 1 / 4 | Cited 8 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Pascual Sánchez‐Juan: h-index 17 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40791093) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
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