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Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease
Davidson MH, Szarek M, Scheltens P, Vijverberg E, Hsieh A, Ditmarsch M, Kling D, Curcio D et al.. The journal of prevention of Alzheimer's disease, 2025-10-17
Topic: Brain proteins, microglia and lab models
Results The analysis population consisted of 1535 (61 %) of the 2530 BROADWAY participants. Baseline p-tau217 levels varied significantly by ApoE subgroups, with ApoE4 carriers generally having higher concentrations and ApoE4/E4 participants exhibiting the highest median concentration (0.56 pg/mL). Obicetrapib significantly attenuated p-tau217 increases compared to placebo (adjusted mean 2.09 % vs 4.94 %; P = 0.025). Furthermore, among ApoE4/E4 participants, there was a 7.81 % adjusted mean decrease in p-tau217 with obicetrapib compared to a 12.67 % increase with placebo, representing a 20.48 % treatment difference (P = 0.010). Positive trends were observed across secondary biomarkers, with obicetrapib also significantly limiting increases in the p-tau217/Aβ42:40 ratio compared to placebo (2.51 % vs 6.55 %; P = 0.004). In addition, among ApoE4/E4 participants, obicetrapib demonstrated significant effects on GFAP (-6.39 % vs +8.85 %; P = 0.006) and NfL (-10.49 % vs +6.82 %; P = 0.020). Conclusions Obicetrapib significantly slowed AD biomarker progression over 12 months in participants with ASCVD, with the greatest effects in ApoE4 carriers. Among ApoE4/E4 participants, obicetrapib reduced p-tau217 levels by a placebo-adjusted 20.48 % and demonstrated consistent effects across multiple AD biomarkers. These findings represent the first demonstration of an oral intervention capable of reducing both beta-amyloid and tau pathology biomarkers in ApoE4 carriers, offering a potential preventive strategy for this high-risk population who currently have no effective prevention options.
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APA 7th
Davidson, M. H., Szarek, M., Scheltens, P., Vijverberg, E., Hsieh, A., Ditmarsch, M., et al. (2026). Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease. The journal of prevention of Alzheimer's disease. https://doi.org/10.1016/j.tjpad.2025.100394
Vancouver
Davidson MH, Szarek M, Scheltens P, Vijverberg E, Hsieh A, Ditmarsch M, et al. Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease. The journal of prevention of Alzheimer's disease. 2026. doi:10.1016/j.tjpad.2025.100394. PMID: 41109840.
BibTeX
@article{davidson2026-41109840,
author = {Davidson, M. H. and Szarek, M. and Scheltens, P. and Vijverberg, E. and Hsieh, A. and Ditmarsch, M. and Kling, D. and Curcio, D. and others},
title = {{Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2026},
doi = {10.1016/j.tjpad.2025.100394},
pmid = {41109840},
url = {https://doi.org/10.1016/j.tjpad.2025.100394}
}
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.
Key findings
- Results The analysis population consisted of 1535 (61 %) of the 2530 BROADWAY participants.
- Baseline p-tau217 levels varied significantly by ApoE subgroups, with ApoE4 carriers generally having higher concentrations and ApoE4/E4 participants exhibiting the highest median concentration (0.56 pg/mL).
- Obicetrapib significantly attenuated p-tau217 increases compared to placebo (adjusted mean 2.09 % vs 4.94 %; P = 0.025).
- Furthermore, among ApoE4/E4 participants, there was a 7.81 % adjusted mean decrease in p-tau217 with obicetrapib compared to a 12.67 % increase with placebo, representing a 20.48 % treatment difference (P = 0.010).
- Positive trends were observed across secondary biomarkers, with obicetrapib also significantly limiting increases in the p-tau217/Aβ42:40 ratio compared to placebo (2.51 % vs 6.55 %; P = 0.004).
Why it matters
In a clinical trial of people with cardiovascular disease, obicetrapib slowed the rise in Alzheimer's blood biomarkers over 12 months, with the largest effects in ApoE4 carriers. The findings are described as the first demonstration of an oral intervention affecting these biomarkers, but the study did not measure whether this changes dementia outcomes.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designclinical trial
- Evidence strengthHigh
How this study scored 63/100
Published in a peer-reviewed journal, and it is a large phase 3 trial. Scored zero for sample size and effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | 0 / 4 | The Journal of Prevention of Alzheimer s Disease: journal h-index 63 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| 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 | 5 / 5 | 2026 — within 1 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| Times cited | 2 / 7 | Cited 12 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 6.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 12 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author John J.P. Kastelein: h-index 167 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Imperial College London: institution h-index 1,744 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 4 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41109840) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.tjpad.2025.100394
- PubMed: 41109840
- Original source →
- Free full text: The Journal of Prevention of Alzheimer s Disease →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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