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Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial
Pontecorvo MJ, Lu M, Burnham SC, Schade AE, Dage JL, Shcherbinin S, Collins EC, Sims JR et al.. JAMA neurology, 2022-12-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To analyze the association of donanemab treatment with plasma biomarkers associated with Alzheimer disease. Results In TRAILBLAZER-ALZ, 272 participants (mean [SD] age, 75.2 [5.5] years; 145 [53.3%] female) were randomized. Plasma levels of phosphorylated tau217 (pTau217) and glial fibrillary acidic protein were significantly lower with donanemab treatment compared with placebo as early as 12 weeks after the start of treatment (least square mean change difference vs placebo, -0.04 [95% CI, -0.07 to -0.02]; P = .002 and -0.04 [95% CI, -0.07 to -0.01]; P = .01, respectively). No significant differences in plasma levels of amyloid-β 42/40 and neurofilament light chain were observed between treatment arms at the end of treatment. Changes in plasma pTau217 and glial fibrillary acidic protein were significantly correlated with the Centiloid percent change in amyloid (Spearman rank correlation coefficient [R] = 0.484 [95% CI, 0.359-0.592]; P Conclusions and relevance Significant reductions in plasma biomarkers pTau217 and glial fibrillary acidic protein compared with placebo were observed following donanemab treatment in patients with early symptomatic Alzheimer disease.
Key findings
- Objective To analyze the association of donanemab treatment with plasma biomarkers associated with Alzheimer disease.
- Results In TRAILBLAZER-ALZ, 272 participants (mean [SD] age, 75.2 [5.5] years; 145 [53.3%] female) were randomized.
- Plasma levels of phosphorylated tau217 (pTau217) and glial fibrillary acidic protein were significantly lower with donanemab treatment compared with placebo as early as 12 weeks after the start of treatment (least square mean change difference vs placebo, -0.04 [95% CI, -0.07 to -0.02]; P = .002 and -0.04 [95% CI, -0.07 to -0.01]; P = .01, respectively).
- No significant differences in plasma levels of amyloid-β 42/40 and neurofilament light chain were observed between treatment arms at the end of treatment.
- Changes in plasma pTau217 and glial fibrillary acidic protein were significantly correlated with the Centiloid percent change in amyloid (Spearman rank correlation coefficient [R] = 0.484 [95% CI, 0.359-0.592]; P < .001 and R = 0.453 [95% CI, 0.306-0.579]; P < .001, respectively) following treatment.
Why it matters
In this exploratory secondary analysis of the TRAILBLAZER-ALZ randomized trial, which randomized 272 people with early symptomatic Alzheimer disease, blood levels of pTau217 and glial fibrillary acidic protein were significantly lower with donanemab than with placebo "as early as 12 weeks after the start of treatment", and those changes were correlated with the percent change in amyloid. Blood amyloid-β 42/40 and neurofilament light chain showed "no significant differences" between arms at the end of treatment. This record reports blood-marker changes only: it does not say whether memory or daily function changed, and it is not evidence that the treatment cures or prevents Alzheimer's disease.
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Study details
- Participants1,955
- Effect size53.3%
- Evidence strengthHigh
How this study scored 82/100
Published in a leading specialty journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,955 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 5 / 7 | Cited 261 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 43.5 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 5 / 6 | Cited 27.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 34 other studies in this library |
| Still being cited | 4 / 4 | Cited 208 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Mark A. Mintun: h-index 131 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Indiana University School of Medicine: institution h-index 784 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 36251300) |
| Free to read | 2 / 2 | Free to read |
| Total | 82 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2022.3392
- PubMed: 36251300
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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
Pontecorvo, M. J., Lu, M., Burnham, S. C., Schade, A. E., Dage, J. L., Shcherbinin, S., et al. (2022). Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial. JAMA neurology. https://doi.org/10.1001/jamaneurol.2022.3392
Vancouver
Pontecorvo MJ, Lu M, Burnham SC, Schade AE, Dage JL, Shcherbinin S, et al. Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial. JAMA neurology. 2022. doi:10.1001/jamaneurol.2022.3392. PMID: 36251300.
BibTeX
@article{pontecorvo2022-36251300,
author = {Pontecorvo, M. J. and Lu, M. and Burnham, S. C. and Schade, A. E. and Dage, J. L. and Shcherbinin, S. and Collins, E. C. and Sims, JR. and others},
title = {{Association of Donanemab Treatment With Exploratory Plasma Biomarkers in Early Symptomatic Alzheimer Disease: A Secondary Analysis of the TRAILBLAZER-ALZ Randomized Clinical Trial}},
journal = {JAMA neurology},
year = {2022},
doi = {10.1001/jamaneurol.2022.3392},
pmid = {36251300},
url = {https://doi.org/10.1001/jamaneurol.2022.3392}
}
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