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Active amyloid beta immunization ameliorates synapse loss and phosphorylated-tau accumulation around remaining plaques for up to 14 years after treatment
Simzer E, McGeachan RI, Tulloch J, Tzioras M, Smith C, Nicoll JA, Boche D, Spires-Jones TL.. medRxiv, 2026-08-11
Topic: Disease mechanisms in lab and animal studies
Amyloid plaques, one of the defining features of Alzheimer’s disease, are associated with synapse loss and accumulation of pathological tau in dystrophic neurites and reactive glia in their immediate vicinity. Anti-amyloid-β immunotherapies have been shown to effectively remove a large proportion of plaques from the brain, but whether immunotherapies reduce pathological changes around remaining plaques or plaques that emerge after treatment remains unknown. We examined amyloid plaques, synapses, astrocytes, and phosphorylated tau in post-mortem brain tissue from people with Alzheimer’s disease who received Amyloid-β42 immunization in the AN1792 trial (Elan Pharmaceuticals), non-immunized or placebo-treated people with Alzheimer’s disease, and neurologically healthy controls. In non-vaccinated individuals, we observe plaque-associated synapse loss, phospho-tau accumulation, and astrogliosis as previously reported. People who received Amyloid-β 42 vaccination had reduced pathology up to 14 years after receiving the vaccine including ameliorated plaque-associated synapse loss, less accumulation of phospho-tau around plaques (AT8 and pTau217), lower levels of astrogliosis, and lower levels of phospho-tau associated with synapses. These data indicate that anti-amyloid active vaccines may have lasting beneficial effects even around remaining plaques or plaques formed after immunization.
Key findings
- Amyloid plaques, one of the defining features of Alzheimer’s disease, are associated with synapse loss and accumulation of pathological tau in dystrophic neurites and reactive glia in their immediate vicinity.
- People who received Amyloid-β 42 vaccination had reduced pathology up to 14 years after receiving the vaccine including ameliorated plaque-associated synapse loss, less accumulation of phospho-tau around plaques (AT8 and pTau217), lower levels of astrogliosis, and lower levels of phospho-tau associated with synapses.
- These data indicate that anti-amyloid active vaccines may have lasting beneficial effects even around remaining plaques or plaques formed after immunization.
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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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Simzer, E., McGeachan, R. I., Tulloch, J., Tzioras, M., Smith, C., Nicoll, J. A., et al. (2026). Active amyloid beta immunization ameliorates synapse loss and phosphorylated-tau accumulation around remaining plaques for up to 14 years after treatment. medRxiv. https://doi.org/10.64898/2026.08.10.26359862
Vancouver
Simzer E, McGeachan RI, Tulloch J, Tzioras M, Smith C, Nicoll JA, et al. Active amyloid beta immunization ameliorates synapse loss and phosphorylated-tau accumulation around remaining plaques for up to 14 years after treatment. medRxiv. 2026. doi:10.64898/2026.08.10.26359862.
BibTeX
@article{simzer2026-c4ebe54d,
author = {Simzer, E. and McGeachan, R. I. and Tulloch, J. and Tzioras, M. and Smith, C. and Nicoll, J. A. and Boche, D. and Spires-Jones, T. L.},
title = {{Active amyloid beta immunization ameliorates synapse loss and phosphorylated-tau accumulation around remaining plaques for up to 14 years after treatment}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.08.10.26359862},
url = {https://doi.org/10.64898/2026.08.10.26359862}
}