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A plasma biomarker panel for detecting early amyloid-β accumulation and its changes in middle-aged cognitively unimpaired individuals at risk for Alzheimer's disease
Armand González-Escalante, Marta Milà-Alomà, Wagner S Brum, Nicholas J Ashton, Paula Ortiz-Romero, Mahnaz Shekari, Marta Del Campo, Federica Anastasi et al.. EBioMedicine, 2025-05-24
Topic: Plasma and spinal-fluid biomarkers
We included 400 middle-aged CU participants, of whom 135 (33.8%) were CSF Aβ-positive. All plasma biomarkers differed between Aβ-positive and -negative individuals, with plasma Aβ42/40, p-tau217, p-tau181/Aβ42, and p-tau217/Aβ42 showing the best performance in detecting A+ CU individuals. However, plasma Aβ42/40 was sensitive to random variability. Plasma p-tau217/Aβ42 had the highest performance in detecting PET A+ individuals (AUC = 0.94). All baseline plasma biomarkers were associated with longitudinal increases in Aβ deposition (mean follow-up [SD]: 3.27 ± 0.5). Longitudinal changes in plasma p-tau217 and p-tau217/Aβ42 were associated with concurrent changes in Aβ (both CSF and PET) and soluble tau pathology. In CU individuals, several plasma biomarkers at baseline detect Aβ accumulation and are associated with its short-term change. Plasma p-tau217, and p-tau217/Aβ42 longitudinal changes reflect concurrent Aβ accumulation during this period. These findings help enrich studies in CU individuals at risk of progressing to AD. FUNDING: ERC-2020-STG (Grant agreement No. 948677); ERA PerMed-ERA NET and the Generalitat de Catalunya (SLD077/21/000001); PI19/00155; PI22/00456, LCF/BQ/PR21/11840004.
Key findings
- We included 400 middle-aged CU participants, of whom 135 (33.8%) were CSF Aβ-positive.
- All plasma biomarkers differed between Aβ-positive and -negative individuals, with plasma Aβ42/40, p-tau217, p-tau181/Aβ42, and p-tau217/Aβ42 showing the best performance in detecting A+ CU individuals.
- However, plasma Aβ42/40 was sensitive to random variability.
- Plasma p-tau217/Aβ42 had the highest performance in detecting PET A+ individuals (AUC = 0.94).
- All baseline plasma biomarkers were associated with longitudinal increases in Aβ deposition (mean follow-up [SD]: 3.27 ± 0.5).
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Study details
- Study designcross-sectional
- Participants400
- Effect size33.8%; AUC = 0.94
- Evidence strengthModerate
How this study scored 68/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for randomised / 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, multi-centre collaboration and free to read, so those were left out: it earned 38 of the 56 points we could judge it on, which is 68 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (EBioMedicine) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2 / 4 | 400 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40414160) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 38 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 38 of the 56 points we could judge it on is 68 out of 100. |
| Total | 68 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
González-Escalante, A., Milà-Alomà, M., Brum, W. S., Ashton, N. J., Ortiz-Romero, P., Shekari, M., et al. (2025). A plasma biomarker panel for detecting early amyloid-β accumulation and its changes in middle-aged cognitively unimpaired individuals at risk for Alzheimer's disease. EBioMedicine. https://doi.org/10.1016/j.ebiom.2025.105741
Vancouver
González-Escalante A, Milà-Alomà M, Brum WS, Ashton NJ, Ortiz-Romero P, Shekari M, et al. A plasma biomarker panel for detecting early amyloid-β accumulation and its changes in middle-aged cognitively unimpaired individuals at risk for Alzheimer's disease. EBioMedicine. 2025. doi:10.1016/j.ebiom.2025.105741. PMID: 40414160.
BibTeX
@article{gonzalezescalante2025-40414160,
author = {González-Escalante, Armand and Milà-Alomà, Marta and Brum, Wagner S and Ashton, Nicholas J and Ortiz-Romero, Paula and Shekari, Mahnaz and Del Campo, Marta and Anastasi, Federica and others},
title = {{A plasma biomarker panel for detecting early amyloid-β accumulation and its changes in middle-aged cognitively unimpaired individuals at risk for Alzheimer's disease}},
journal = {EBioMedicine},
year = {2025},
doi = {10.1016/j.ebiom.2025.105741},
pmid = {40414160},
url = {https://doi.org/10.1016/j.ebiom.2025.105741}
}
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