Serpin A3 is Increased in Cerebral Amyloid Angiopathy and ARIA
Ventura-Antunes L, Janve VA, Womble N, Weasler CJ, Hai SA, Brula H, Mobley BC, Hohman TJ et al.. bioRxiv, 2026-10-24
Topic: Inflammation, microglia and astrocytes
Vascular pathology is an important contributor to dementia, and astrocyte dysfunction is increasingly recognized as a key mediator of cerebrovascular injury. Serpin A3 is a well-known marker of reactive astrocytes, yet its role in vascular degeneration in cerebral amyloid angiopathy and Alzheimer’s disease remains poorly defined. We combined analyses of single nucleus transcriptomic datasets with western blotting and quantitative two- and three-dimensional microscopy of human brain tissue to characterize Serpin A3 expression, distribution, cellular sources, and neuropathological correlates in the human brain. Serpin A3 protein abundance was increased in cases with cerebral amyloid angiopathy and Alzheimer’s disease compared to neurological controls, both by western blot and quantitative microscopy. The tissue distribution of Serpin A3 was heterogeneous and was predominantly within astrocytes associated with degenerating arterioles. Serpin A3 was also detected around parenchymal β-amyloid plaques. In a postmortem case of active and severe lecanemab-associated amyloid-related imaging abnormalities, light sheet microscopy revealed prominent Serpin A3 immunoreactivity around inflamed, dilated vessels and microhemorrhages, with Serpin A3 levels higher those found in the Cerebral Amyloid Angiopathy cases. These findings identify Serpin A3 as a marker of cerebrovascular injury and astrocyte-driven inflammatory responses in cerebral amyloid angiopathy.
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APA 7th
Ventura-Antunes, L., Janve, V. A., Womble, N., Weasler, C. J., Hai, S. A., Brula, H., et al. (2026). Serpin A3 is Increased in Cerebral Amyloid Angiopathy and ARIA. bioRxiv. https://doi.org/10.64898/2026.10.19.759840
Vancouver
Ventura-Antunes L, Janve VA, Womble N, Weasler CJ, Hai SA, Brula H, et al. Serpin A3 is Increased in Cerebral Amyloid Angiopathy and ARIA. bioRxiv. 2026. doi:10.64898/2026.10.19.759840.
BibTeX
@article{venturaantunes2026-4f28fca6,
author = {Ventura-Antunes, L. and Janve, V. A. and Womble, N. and Weasler, C. J. and Hai, S. A. and Brula, H. and Mobley, B. C. and Hohman, T. J. and others},
title = {{Serpin A3 is Increased in Cerebral Amyloid Angiopathy and ARIA}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.19.759840},
url = {https://doi.org/10.64898/2026.10.19.759840}
}
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Key findings
- Serpin A3 protein abundance was increased in cases with cerebral amyloid angiopathy and Alzheimer’s disease compared to neurological controls, both by western blot and quantitative microscopy.
- The tissue distribution of Serpin A3 was heterogeneous and was predominantly within astrocytes associated with degenerating arterioles.
- In a postmortem case of active and severe lecanemab-associated amyloid-related imaging abnormalities, light sheet microscopy revealed prominent Serpin A3 immunoreactivity around inflamed, dilated vessels and microhemorrhages, with Serpin A3 levels higher those found in the Cerebral Amyloid Angiopathy cases.
- These findings identify Serpin A3 as a marker of cerebrovascular injury and astrocyte-driven inflammatory responses in cerebral amyloid angiopathy.
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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 randomized / 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 multicenter 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter 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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