Home › Research › Treatments
Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab
Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, Klunk WE, Ashford E et al.. Archives of neurology, 2011-10-10
Topic: Amyloid, tau and blood-test diagnosis
Background Gantenerumab is a fully human anti-Aβ monoclonal antibody in clinical development for the treatment of Alzheimer disease (AD). Objectives To investigate whether treatment with gantenerumab leads to a measurable reduction in the level of Aβ amyloid in the brain and to elucidate the mechanism of amyloid reduction. Design A multicenter, randomized, double-blind, placebo-controlled, ascending-dose positron emission tomographic study. Additionally, ex vivo studies of human brain slices from an independent sample of patients who had AD were performed. Setting Three university medical centers. Patients Patients with mild-to-moderate AD. Intervention Two consecutive cohorts of patients received 2 to 7 infusions of intravenous gantenerumab (60 or 200 mg) or placebo every 4 weeks. Brain slices from patients who had AD were coincubated with gantenerumab at increasing concentrations and with human microglial cells. Main outcome measures Percent change in the ratio of regional carbon 11-labeled Pittsburgh Compound B retention in vivo and semiquantitative assessment of gantenerumab-induced phagocytosis ex vivo. Results Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis. The mean (95% CI) percent change from baseline difference relative to placebo (n = 4) in cortical brain amyloid level was -15.6% (95% CI, -42.7 to 11.6) for the 60-mg group (n = 6) and -35.7% (95% CI, -63.5 to -7.9) for the 200-mg group (n = 6). Two patients in the 200-mg group showed transient and focal areas of inflammation or vasogenic edema on magnetic resonance imaging scans at sites with the highest level of amyloid reduction. Gantenerumab induced phagocytosis of human amyloid in a dose-dependent manner ex vivo. Conclusion Gantenerumab treatment resulted in a dose-dependent reduction in brain amyloid level, possibly through an effector cell-mediated mechanism of action.
Key findings
- Results Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis.
Why it matters
In a small placebo-controlled study of 16 people with mild-to-moderate Alzheimer's disease, the antibody gantenerumab lowered brain amyloid on PET scans by about 36% more than placebo at the 200 mg dose, while the 60 mg result was uncertain and could have been no effect. Two of the six people on 200 mg had temporary, localised inflammation or swelling on brain MRI, in the areas where the most amyloid was cleared, and lab tests on donated brain tissue suggested the antibody works by helping immune cells engulf amyloid. The study measured amyloid only, not memory or daily function, so it does not show whether the drug helps patients.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Effect size15.6%; 35.7%
- Evidence strengthHigh
How this study scored 72/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (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 | 1 / 5 | 2012 — within 20 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 433 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 5 / 6 | Cited 23.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 39 other studies in this library |
| Still being cited | 3 / 4 | Cited 69 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Susanne Ostrowitzki: h-index 25 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Roche (Switzerland): institution h-index 638 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21987394) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 72 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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
Ostrowitzki, S., Deptula, D., Thurfjell, L., Barkhof, F., Bohrmann, B., Brooks, D. J., et al. (2012). Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Archives of neurology. https://doi.org/10.1001/archneurol.2011.1538
Vancouver
Ostrowitzki S, Deptula D, Thurfjell L, Barkhof F, Bohrmann B, Brooks DJ, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Archives of neurology. 2012. doi:10.1001/archneurol.2011.1538. PMID: 21987394.
BibTeX
@article{ostrowitzki2012-21987394,
author = {Ostrowitzki, S. and Deptula, D. and Thurfjell, L. and Barkhof, F. and Bohrmann, B. and Brooks, D. J. and Klunk, W. E. and Ashford, E. and others},
title = {{Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab}},
journal = {Archives of neurology},
year = {2012},
doi = {10.1001/archneurol.2011.1538},
pmid = {21987394},
url = {https://doi.org/10.1001/archneurol.2011.1538}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
39 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Treatments
Also tagged “double-blind”
783 studies in the library carry the topic tag “double-blind”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 783 tagged studies.