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A plasma protein signature for cerebral amyloid angiopathy
Alpana Singh, Marisa N. Denkinger, Antoine Leuzy, Kari Dieckhoff, Jame Liu, Tainá M. Marques, Edwin S. Monuki, Craig Stark et al.. Acta Neuropathologica, 2026-05-20
Topic: Amyloid, tau and blood-test diagnosis
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by the deposition of amyloid-β (Aβ) in the walls of leptomeningeal and cortical blood vessels that increases risk of intracerebral hemorrhages and progressive cognitive decline. More than 90% of individuals with Alzheimer's disease (AD) exhibit some level of CAA. Notably, in the new era of disease-modifying treatments for AD, CAA is a significant risk factor for amyloid-related imaging abnormalities (ARIA), an adverse event associated with anti-amyloid treatments. Therefore, there is great need for accessible, reliable and accurate in vivo biomarkers (e.g., blood-based) to improve antemortem identification of CAA that would improve risk stratification and reduce symptomatic ARIA. In this study, we employed the Nucleic Acid-Linked Immuno-Sandwich Assay (NULISA™) central nervous system panel for exploratory biomarker quantification in antemortem plasma of participants with neuropathological assessments for CAA from the Banner Sun Health Research Institute Brain and Body Donation Program (N = 251) and independently validated in the University of California Irvine Alzheimer Disease Research Center cohort (N = 110). We evaluated the differential protein expression in antemortem plasma sample taken < 5 years (mean 1.76 ± 1.3) from death using a logistic regression model. We further compared multi-biomarker models and found that a combination of CRP, IL4, CCL11, NPY and PDLIM5, plus demographic covariates showed an area under the curve (AUC) of 0.90 (95% CI 0.86-0.94) to identify neuropathologically confirmed CAA in the discovery cohort. In our independent replication, the antemortem plasma signature performed better than the basic demographics model showing a potential to predict CAA. The exploration and validation in antemortem plasma indicate that a multi-analyte panel, when combined with in vivo blood biomarkers for AD pathology, may be capable of identifying the presence of CAA and could have an meaningful impact on the clinical evaluation of patients under the investigation for cognitive decline. Further developments in biomarkers for this condition are crucial so that CAA identification could inform treatment decisions by highlighting ARIA risk.
Key findings
- Notably, in the new era of disease-modifying treatments for AD, CAA is a significant risk factor for amyloid-related imaging abnormalities (ARIA), an adverse event associated with anti-amyloid treatments.
- The exploration and validation in antemortem plasma indicate that a multi-analyte panel, when combined with in vivo blood biomarkers for AD pathology, may be capable of identifying the presence of CAA and could have an meaningful impact on the clinical evaluation of patients under the investigation for cognitive decline.
Why it matters
This study used a plasma protein panel to explore biomarkers of cerebral amyloid angiopathy, a condition present in more than 90% of people with Alzheimer's disease and a significant risk factor for ARIA with anti-amyloid treatments. The authors report that a multi-analyte panel combined with blood biomarkers for Alzheimer's pathology may be able to identify CAA, which could improve risk stratification and reduce symptomatic ARIA.
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Study details
- Participants251
- Evidence strengthModerate
How this study scored 51/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta Neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” 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 | 2 / 4 | 251 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Nicholas James Ashton: h-index 91 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42162487) |
| Free to read | 2 / 2 | Free to read |
| Total | 51 / 100 | — |
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Read the original
- DOI: 10.1007/s00401-026-03030-5
- PubMed: 42162487
- Original source →
- Free full text: Acta Neuropathologica →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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
Singh, A., Denkinger, M. N., Leuzy, A., Dieckhoff, K., Liu, J., Marques, T. M., et al. (2026). A plasma protein signature for cerebral amyloid angiopathy. Acta Neuropathologica. https://doi.org/10.1007/s00401-026-03030-5
Vancouver
Singh A, Denkinger MN, Leuzy A, Dieckhoff K, Liu J, Marques TM, et al. A plasma protein signature for cerebral amyloid angiopathy. Acta Neuropathologica. 2026. doi:10.1007/s00401-026-03030-5. PMID: 42162487.
BibTeX
@article{singh2026-42162487,
author = {Singh, Alpana and Denkinger, Marisa N. and Leuzy, Antoine and Dieckhoff, Kari and Liu, Jame and Marques, Tainá M. and Monuki, Edwin S. and Stark, Craig and others},
title = {{A plasma protein signature for cerebral amyloid angiopathy}},
journal = {Acta Neuropathologica},
year = {2026},
doi = {10.1007/s00401-026-03030-5},
pmid = {42162487},
url = {https://doi.org/10.1007/s00401-026-03030-5}
}
Studies this one cites
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