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Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology
Przemysław R Kac, Armand González-Escalante, Marta Milà-Alomà, Nicholas J Ashton, Mahnaz Shekari, Paula Ortiz-Romero, Michael Turton, Peter Harrison et al.. Journal of neurology, 2025-12-25
Topic: Plasma and spinal-fluid biomarkers
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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APA 7th
Kac, P. R., González-Escalante, A., Milà-Alomà, M., Ashton, N. J., Shekari, M., Ortiz-Romero, P., et al. (2025). Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology. Journal of neurology. https://doi.org/10.1007/s00415-025-13572-5
Vancouver
Kac PR, González-Escalante A, Milà-Alomà M, Ashton NJ, Shekari M, Ortiz-Romero P, et al. Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology. Journal of neurology. 2025. doi:10.1007/s00415-025-13572-5. PMID: 41447416.
BibTeX
@article{kac2025-41447416,
author = {Kac, Przemysław R and González-Escalante, Armand and Milà-Alomà, Marta and Ashton, Nicholas J and Shekari, Mahnaz and Ortiz-Romero, Paula and Turton, Michael and Harrison, Peter and others},
title = {{Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology}},
journal = {Journal of neurology},
year = {2025},
doi = {10.1007/s00415-025-13572-5},
pmid = {41447416},
url = {https://doi.org/10.1007/s00415-025-13572-5}
}
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Key findings
- 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.
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Study details
- Participants317
- Evidence strengthLow
How this study scored 52/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multicenter collaboration and free to read, so those were left out: it earned 29 of the 56 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” 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 | 2 / 4 | 317 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41447416) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 29 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 29 of the 56 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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