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Intravenous anti-Aβ immunotherapy acutely increases cerebral amyloid angiopathy and vascular damages in APOE4 mice
Pikus P, Healey GS, Xia E, Shautidze G, Siddapureddy N, Lee Y, Albanese C, Rodriguez O et al.. bioRxiv, 2026-02-11
Topic: Inflammation, microglia and astrocytes
Anti-Aβ immunotherapies for Alzheimer’s Disease (AD) have high rates of amyloid-related imaging abnormalities (ARIA), an adverse side effect with markedly higher rates in APOE4 carriers. We developed a mouse model of ARIA centered on human APOE3 and APOE4 genotypes with amyloidosis (5xFAD transgene) and microglia tagged with green fluorescent protein (from the CX3CR1 promoter). We measured acute changes following a single intravenous treatment with 3D6 anti-Aβ immunotherapy. Across 82 mice, APOE4 mice showed stepwise reductions in the number of plaques from one to ten days, with significant reductions in the subiculum (48%) and thalamus (40%) at ten days. There was no significant reduction in APOE3 mice. There was a concomitant significant increase in deposition of cerebral amyloid angiopathy (CAA) in APOE4 mice at one (76%) and three (51%) days in leptomeningeal vessels. The increased CAA correlated with a significant 189% increase in Aβ within microglia of APOE4 (but not APOE3 ) mice at one day. Smooth muscle actin staining showed significant 58% reduction near CAA. MRI analysis revealed a significant 32% increase in microhemorrhages ten days following treatment. These data demonstrate an APOE4 -specific redistribution of parenchymal amyloid to CAA by 3D6 within days, leading to increased vascular damages associated with ARIA.
Key findings
- Across 82 mice, APOE4 mice showed stepwise reductions in the number of plaques from one to ten days, with significant reductions in the subiculum (48%) and thalamus (40%) at ten days.
- There was no significant reduction in APOE3 mice.
- There was a concomitant significant increase in deposition of cerebral amyloid angiopathy (CAA) in APOE4 mice at one (76%) and three (51%) days in leptomeningeal vessels.
- The increased CAA correlated with a significant 189% increase in Aβ within microglia of APOE4 (but not APOE3 ) mice at one day.
- Smooth muscle actin staining showed significant 58% reduction near CAA.
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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Preprint — not yet peer-reviewed.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 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 (bioRxiv) |
| 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 | Laboratory or animal study (title names “mice”) — scores zero |
| 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
Pikus, P., Healey, G. S., Xia, E., Shautidze, G., Siddapureddy, N., Lee, Y., et al. (2026). Intravenous anti-Aβ immunotherapy acutely increases cerebral amyloid angiopathy and vascular damages in APOE4 mice. bioRxiv. https://doi.org/10.64898/2026.02.09.704876
Vancouver
Pikus P, Healey GS, Xia E, Shautidze G, Siddapureddy N, Lee Y, et al. Intravenous anti-Aβ immunotherapy acutely increases cerebral amyloid angiopathy and vascular damages in APOE4 mice. bioRxiv. 2026. doi:10.64898/2026.02.09.704876.
BibTeX
@article{pikus2026-5846ffcd,
author = {Pikus, P. and Healey, G. S. and Xia, E. and Shautidze, G. and Siddapureddy, N. and Lee, Y. and Albanese, C. and Rodriguez, O. and others},
title = {{Intravenous anti-Aβ immunotherapy acutely increases cerebral amyloid angiopathy and vascular damages in APOE4 mice}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.02.09.704876},
url = {https://doi.org/10.64898/2026.02.09.704876}
}
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