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Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial
Wagemann O, Liu H, Wang G, Shi X, Bittner T, Scelsi MA, Farlow MR, Clifford DB et al.. JAMA neurology, 2024-06-01
Topic: Amyloid, tau and blood-test diagnosis
Plain-language summary
Importance Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). Objective To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. Design, setting, and participants From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD. Carriers of gene variants were assigned 3:1 to either drug or placebo. The present analysis was conducted from April to June 2023. DIAN-TU-001 spans 25 study sites in 7 countries. Biofluids and neuroimaging from carriers of DIAD gene variants in the gantenerumab, solanezumab, and placebo groups were analyzed. Interventions In 2016, initial dosing of gantenerumab, 225 mg (subcutaneously every 4 weeks) was increased every 8 weeks up to 1200 mg. In 2017, initial dosing of solanezumab, 400 mg (intravenously every 4 weeks) was increased up to 1600 mg every 4 weeks. Main outcomes and measures Longitudinal changes in CSF levels of neurogranin, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), glial fibrillary acidic protein (GFAP), neurofilament light protein (NfL), and plasma levels of GFAP and NfL. Results Of 236 eligible participants screened, 43 were excluded. A total of 142 participants (mean [SD] age, 44 [10] years; 72 female [51%]) were included in the study (gantenerumab, 52 [37%]; solanezumab, 50 [35%]; placebo, 40 [28%]). Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] β = -242.43 [48.04] pg/mL; P Conclusions and relevance This randomized clinical trial supports the importance of fibrillar amyloid reduction in multiple AD-related processes of neuroinflammation and neurodegeneration in CSF and plasma in DIAD. Additional studies of antiaggregated amyloid therapies in sporadic AD and DIAD are needed to determine the utility of nonamyloid biomarkers in determining disease modification. Trial registration ClinicalTrials.gov Identifier: NCT04623242.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Wagemann, O., Liu, H., Wang, G., Shi, X., Bittner, T., Scelsi, M. A., et al. (2024). Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial. JAMA neurology. https://doi.org/10.1001/jamaneurol.2024.0991
Vancouver
Wagemann O, Liu H, Wang G, Shi X, Bittner T, Scelsi MA, et al. Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial. JAMA neurology. 2024. doi:10.1001/jamaneurol.2024.0991. PMID: 38683602.
BibTeX
@article{wagemann2024-38683602,
author = {Wagemann, O. and Liu, H. and Wang, G. and Shi, X. and Bittner, T. and Scelsi, M. A. and Farlow, M. R. and Clifford, D. B. and others},
title = {{Downstream Biomarker Effects of Gantenerumab or Solanezumab in Dominantly Inherited Alzheimer Disease: The DIAN-TU-001 Randomized Clinical Trial}},
journal = {JAMA neurology},
year = {2024},
doi = {10.1001/jamaneurol.2024.0991},
pmid = {38683602},
url = {https://doi.org/10.1001/jamaneurol.2024.0991}
}
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 Of 236 eligible participants screened, 43 were excluded.
- Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] β = -242.43 [48.04] pg/mL; P < .001); reduced plasma GFAP level at year 1 (mean [SD] β = -0.02 [0.01] ng/mL; P = .02), year 2 (mean [SD] β = -0.03 [0.01] ng/mL; P = .002), and year 4 (mean [SD] β = -0.06 [0.02] ng/mL; P < .001); and increased CSF sTREM2 level at year 2 (mean [SD] β = 1.12 [0.43] ng/mL; P = .01) and year 4 (mean [SD] β = 1.06 [0.52] ng/mL; P = .04).
Why it matters
In people with dominantly inherited Alzheimer disease, the drug gantenerumab reduced a cerebrospinal fluid marker of synaptic damage (neurogranin) compared with placebo. This supports the idea that reducing fibrillar amyloid affects processes related to neuroinflammation and neurodegeneration, though the study looked at biomarkers rather than whether patients felt or functioned better.
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Study details
- Study designlongitudinal study
- Participants142
- Evidence strengthHigh
How this study scored 74/100
Published in a leading specialty journal, and it is a randomized controlled trial. Scored zero for effect reported because the record does not state it.
| 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 randomized 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 142 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 | 2 / 2 | Randomized and blinded or placebo-controlled (as stated in the record) |
| Times cited | 3 / 7 | Cited 37 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 4 / 6 | Cited 8.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 37 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Yoshiki Niimi: h-index 23 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 32 institution(s) in 9 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38683602) |
| Free to read | 2 / 2 | Free to read |
| Total | 74 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2024.0991
- PubMed: 38683602
- 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).
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