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Gantenerumab reduces brain amyloid-β proteoforms: Biochemical evaluation in dominantly inherited Alzheimer disease
Mukherjee S, Barthélemy NR, Atri T, Li Y, Yen D, He Y, Coyle R, Ovod V et al.. medRxiv, 2026-09-29
Topic: Amyloid, tau and blood-test diagnosis
Symptomatic DIAD participants who had been treated for ∼ 4 years with anti-Aβ monoclonal antibodies (gantenerumab, n=4 or solanezumab, n=4) were compared with untreated, symptomatic DIAD mutation carriers (n=40) and with age-relevant non-DIAD controls with modest or no plaque pathology (n=18). Consistent with antemortem Aβ-PET findings in the clinical trial, gantenerumab-treated participant samples showed significantly lower levels of specific Aβ proteoforms (Aβ 42 , Aβ 40 ) in the insoluble plaque associated pool (range: 60-80 % reduction); they also showed lower levels of post-translationally modified Aβ proteoform Aβ 3pGlu in both the insoluble and soluble pool, compared to untreated DIAD participants, but without reaching the levels found in non-DIAD controls. In contrast, brain tissue samples from solanezumab-treated participants did not show significant differences overall in soluble or insoluble levels of Aβ and tau proteoforms in comparison to those from non-treated DIAD individuals. These findings support that amyloid targeting treatment (ATT) with gantenerumab, an antibody that targets fibrillar Aβ, can remove insoluble Aβ from the DIAD brain and also mitigate “downstream” biochemical and pathophysiological changes associated with AD. Recently, passive immunizations using anti-Aβ targeting antibodies have demonstrated slowing of cognitive decline in sporadic AD and possibly in dominantly inherited AD (DIAD). Consistent with antemortem Aβ-PET findings in the clinical trial, gantenerumab significantly decreased specific Aβ (Aβ 42 , Aβ 40 ) proteoforms in the insoluble plaque associated pool (range: 60-80% reduction) compared to the untreated DIAD participants, but without reaching the levels found in the non-DIAD controls. Samples from gantenerumab treated participants also showed significantly lower amount of post-translationally modified Aβ (Aβ 3pGlu ) and regionally lower insoluble phosphorylated tau species (pT181, pT205 and pT208), without apparent differences in insoluble total tau levels. In contrast, solanezumab treatment did not show significant effect on the soluble or insoluble levels of Aβ and tau proteoforms in comparison to samples from non-treated DIAD individuals. Significance These findings support that ATT with gantenerumab, an antibody that targets fibrillar Aβ, can remove insoluble Aβ from the DIAD brain and also mitigate “downstream” biochemical and pathophysiological changes associated with AD.
Key findings
- Symptomatic DIAD participants who had been treated for ∼ 4 years with anti-Aβ monoclonal antibodies (gantenerumab, n=4 or solanezumab, n=4) were compared with untreated, symptomatic DIAD mutation carriers (n=40) and with age-relevant non-DIAD controls with modest or no plaque pathology (n=18).
- Consistent with antemortem Aβ-PET findings in the clinical trial, gantenerumab-treated participant samples showed significantly lower levels of specific Aβ proteoforms (Aβ 42 , Aβ 40 ) in the insoluble plaque associated pool (range: 60-80 % reduction); they also showed lower levels of post-translationally modified Aβ proteoform Aβ 3pGlu in both the insoluble and soluble pool, compared to untreated DIAD participants, but without reaching the levels found in non-DIAD controls.
- In contrast, brain tissue samples from solanezumab-treated participants did not show significant differences overall in soluble or insoluble levels of Aβ and tau proteoforms in comparison to those from non-treated DIAD individuals.
- These findings support that amyloid targeting treatment (ATT) with gantenerumab, an antibody that targets fibrillar Aβ, can remove insoluble Aβ from the DIAD brain and also mitigate “downstream” biochemical and pathophysiological changes associated with AD.
- Recently, passive immunizations using anti-Aβ targeting antibodies have demonstrated slowing of cognitive decline in sporadic AD and possibly in dominantly inherited AD (DIAD).
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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. 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
Mukherjee, S., Barthélemy, N. R., Atri, T., Li, Y., Yen, D., He, Y., et al. (2026). Gantenerumab reduces brain amyloid-β proteoforms: Biochemical evaluation in dominantly inherited Alzheimer disease. medRxiv. https://doi.org/10.64898/2026.09.22.26363432
Vancouver
Mukherjee S, Barthélemy NR, Atri T, Li Y, Yen D, He Y, et al. Gantenerumab reduces brain amyloid-β proteoforms: Biochemical evaluation in dominantly inherited Alzheimer disease. medRxiv. 2026. doi:10.64898/2026.09.22.26363432.
BibTeX
@article{mukherjee2026-09be60d1,
author = {Mukherjee, S. and Barthélemy, N. R. and Atri, T. and Li, Y. and Yen, D. and He, Y. and Coyle, R. and Ovod, V. and others},
title = {{Gantenerumab reduces brain amyloid-β proteoforms: Biochemical evaluation in dominantly inherited Alzheimer disease}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.09.22.26363432},
url = {https://doi.org/10.64898/2026.09.22.26363432}
}
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