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Interim biomarker results for trontinemab, a novel Brainshuttle antibody in development for the treatment of Alzheimer's disease
Klein G, Rabinovici GD, Zetterberg H, et al.. Alzheimer's & Dementia (AAIC 2025 conference abstract), 2025
Topic: Amyloid, tau and blood-test diagnosis
Trontinemab is designed with a molecular 'shuttle' that helps it cross into the brain more efficiently than older anti-amyloid antibodies, aiming for faster plaque removal at lower doses. In this early trial, the highest dose group saw a large drop in brain amyloid (over 100 centiloids on average) within about 7 months, along with meaningful drops in tau and neurodegeneration markers in spinal fluid.
Key findings
- Randomized, double-blind, placebo-controlled Phase Ib/IIa multiple ascending dose design
- 3.6 mg/kg dose group: mean amyloid PET reduction of 107 centiloids at 28 weeks
- 81% of participants (21/26) in the 3.6 mg/kg group fell below the 24-centiloid positivity threshold by 28 weeks (per related company data)
- CSF total tau down 30%, p-tau181 down 34%, neurogranin down 29% at week 25
- ARIA-E reported in under 5% of participants, notably lower than some other anti-amyloid antibodies
Why it matters
Trontinemab is designed with a molecular 'shuttle' that helps it cross into the brain more efficiently than older anti-amyloid antibodies, aiming for faster plaque removal at lower doses. In this early trial, the highest dose group saw a large drop in brain amyloid (over 100 centiloids on average) within about 7 months, along with meaningful drops in tau and neurodegeneration markers in spinal fluid.
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Study details
- Study designphase-2-trial
- Participants13
- Effect sizeMean amyloid PET reduction of 107 centiloids at 28 weeks in the 3.6 mg/kg group (from -89 centiloids at 12 weeks); CSF total tau reduced 30%, p-tau181 reduced 34%, neurogranin reduced 29% by week 25
- Evidence strengthEarly
Limitations
Conference-abstract-level reporting of an early-phase (Ib/IIa), open interim analysis with small per-dose-group sample sizes (as few as 12-13 in the top-dose cohort); no cognitive/functional outcome data included in this report, and full ARIA incidence table not provided in the abstract.
How this study scored 16/100
Conference abstract — not peer-reviewed. It scored 38 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomised / blinded and indexed in PubMed because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, 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 25 of the 66 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (Alzheimer's & Dementia (AAIC 2025 conference abstract)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 8 / 12 | A mid-stage phase 2 trial |
| Strength of evidence | 2 / 5 | Rated “early” in our summary |
| Peer-review validation | 3 / 10 | Conference abstract — not peer-reviewed. Journal string identifies this as a conference abstract or presentation. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 13 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 | 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 | 0 / 6 | No other study in this library cites it |
| 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 | 0 / 2 | No PubMed ID and no DOI — scores zero (not stated in the record — scored 0) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 25 / 66 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 25 of the 66 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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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. This record has no DOI, so the citation leaves it out. 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
Klein, G., Rabinovici, G. D., Zetterberg, H., et al. (2025). Interim biomarker results for trontinemab, a novel Brainshuttle antibody in development for the treatment of Alzheimer's disease. Alzheimer's & Dementia (AAIC 2025 conference abstract).
Vancouver
Klein G, Rabinovici GD, Zetterberg H, et al. Interim biomarker results for trontinemab, a novel Brainshuttle antibody in development for the treatment of Alzheimer's disease. Alzheimer's & Dementia (AAIC 2025 conference abstract). 2025.
BibTeX
@article{klein2025-b9ea469a,
author = {Klein, G. and Rabinovici, G. D. and Zetterberg, H. and others},
title = {{Interim biomarker results for trontinemab, a novel Brainshuttle antibody in development for the treatment of Alzheimer's disease}},
journal = {Alzheimer's \& Dementia (AAIC 2025 conference abstract)},
year = {2025}
}
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