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Dual roles of complement in cerebral amyloid angiopathy: A two-compartment framework across the blood-brain barrier
Yin WM, He LC, Zhu HH, Cao Y, Li AM, Wang YC, Xu YM.. International immunopharmacology, 2026-02-21
Topic: Brain proteins, microglia and lab models
Complement is increasingly recognized as a context-dependent contributor to cerebral amyloid angiopathy (CAA), yet its roles are often discussed without compartmental resolution and are frequently extrapolated from Alzheimer's disease (AD). This review synthesizes evidence from human pathology, multi-omics, and experimental models to delineate how complement activity diverges between the vessel wall/perivascular space (PVS) and the brain parenchyma, and how the two compartments couple when the blood-brain barrier (BBB) is compromised. In the vessel wall/PVS, where Aβ40 deposition coincides with endothelial stress and access to circulating proteins, complement activation can be sustained and may progress to terminal pathway engagement. Available data link membrane attack complex (MAC) formation to vessel wall injury, BBB disruption, microbleeds, and impaired intramural periarterial drainage (IPAD), reinforcing vascular Aβ accumulation. Classical pathway signals are consistently detected in CAA vessels, while lectin pathway co-activation and alternative pathway amplification likely contribute to persistent activation at the vascular interface. In the parenchyma, terminal outputs appear more constrained and pathogenic effects are more often mediated by C1q/C3 opsonization and C3a/C5a receptor signaling that sustains glial inflammatory circuits and synaptic vulnerability, secondarily destabilizing the BBB and facilitating spillover. CAA-related inflammation and anti-Aβ therapy-associated ARIA highlight periods of amplified vascular inflammation that expose these injury programs. Finally, we outline a compartment- and stage-specific therapeutic framework that prioritizes reducing terminal pathway burden and MAC-driven vascular injury while limiting parenchymal inflammatory amplification and preserving early opsonophagocytic clearance, supported by spatial biomarkers and CAA-specific models.
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APA 7th
Yin, W. M., He, L. C., Zhu, H. H., Cao, Y., Li, A. M., Wang, Y. C., et al. (2026). Dual roles of complement in cerebral amyloid angiopathy: A two-compartment framework across the blood-brain barrier. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.116407
Vancouver
Yin WM, He LC, Zhu HH, Cao Y, Li AM, Wang YC, et al. Dual roles of complement in cerebral amyloid angiopathy: A two-compartment framework across the blood-brain barrier. International immunopharmacology. 2026. doi:10.1016/j.intimp.2026.116407. PMID: 41723897.
BibTeX
@article{yin2026-41723897,
author = {Yin, W. M. and He, L. C. and Zhu, H. H. and Cao, Y. and Li, A. M. and Wang, Y. C. and Xu, Y. M.},
title = {{Dual roles of complement in cerebral amyloid angiopathy: A two-compartment framework across the blood-brain barrier}},
journal = {International immunopharmacology},
year = {2026},
doi = {10.1016/j.intimp.2026.116407},
pmid = {41723897},
url = {https://doi.org/10.1016/j.intimp.2026.116407}
}
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 7 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.
Key findings
- Available data link membrane attack complex (MAC) formation to vessel wall injury, BBB disruption, microbleeds, and impaired intramural periarterial drainage (IPAD), reinforcing vascular Aβ accumulation.
- Classical pathway signals are consistently detected in CAA vessels, while lectin pathway co-activation and alternative pathway amplification likely contribute to persistent activation at the vascular interface.
- In the parenchyma, terminal outputs appear more constrained and pathogenic effects are more often mediated by C1q/C3 opsonization and C3a/C5a receptor signaling that sustains glial inflammatory circuits and synaptic vulnerability, secondarily destabilizing the BBB and facilitating spillover.
- CAA-related inflammation and anti-Aβ therapy-associated ARIA highlight periods of amplified vascular inflammation that expose these injury programs.
- Finally, we outline a compartment- and stage-specific therapeutic framework that prioritizes reducing terminal pathway burden and MAC-driven vascular injury while limiting parenchymal inflammatory amplification and preserving early opsonophagocytic clearance, supported by spatial biomarkers and CAA-specific models.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. 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 journal's citation record, 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 25 of the 58 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International immunopharmacology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| 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 | 2 / 2 | Indexed in PubMed (PMID 41723897) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 25 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 25 of the 58 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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