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Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy
Yun Chen, Yizhou A. Liu, Khai M. Nguyen, Junjie Wu, Sihui Song, Kent Lin, Patrick Fernandes Rodrigues, Siling Du et al.. Science, 2026-03-05
Topic: Brain proteins, microglia and lab models
Alzheimer's disease (AD) is the leading cause of dementia and is characterized by progressive amyloid accumulation followed by tau-mediated neurodegeneration. Despite advances in anti-amyloid immunotherapies, important limitations remain, highlighting the need for new therapeutic strategies. Here, we introduce anti-amyloid chimeric antigen receptors expressed in astrocytes (CAR-A) and validate their function in vitro. We show that two CAR-A designs reduce amyloid and associated pathology after plaque formation and prevent early plaque deposition in vivo. Single-nucleus RNA sequencing shows that CAR-A treatment induces a distinct glial response to amyloid pathology involving coordinated activity of astrocytes and microglia. Each construct additionally elicits distinctive, receptor-specific effects in astrocytes or microglia. Together, these findings support the therapeutic potential of CAR-A as a disease-modifying strategy for AD.
Key findings
- Together, these findings support the therapeutic potential of CAR-A as a disease-modifying strategy for AD.
Why it matters
In this study, anti-amyloid chimeric antigen receptors expressed in astrocytes reduced amyloid and associated pathology and prevented early plaque deposition in vivo. The findings support CAR-A as a potential disease-modifying strategy but are early work and do not yet show benefit in people.
Study details
- Evidence strengthLow
How this study scored 55/100
Published in a top-tier journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (Science) |
| Journal's citation record | 4 / 4 | Science: journal h-index 1,754 (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 | 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 | 3 / 7 | Cited 21 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 6 / 6 | Cited 86.9× 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 | 2 / 4 | Cited 21 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Marco Colonna: h-index 172 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41785364) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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
Chen, Y., Liu, Y. A., Nguyen, K. M., Wu, J., Song, S., Lin, K., et al. (2026). Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy. Science. https://doi.org/10.1126/science.ads3972
Vancouver
Chen Y, Liu YA, Nguyen KM, Wu J, Song S, Lin K, et al. Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy. Science. 2026. doi:10.1126/science.ads3972. PMID: 41785364.
BibTeX
@article{chen2026-41785364,
author = {Chen, Yun and Liu, Yizhou A. and Nguyen, Khai M. and Wu, Junjie and Song, Sihui and Lin, Kent and Rodrigues, Patrick Fernandes and Du, Siling and others},
title = {{Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy}},
journal = {Science},
year = {2026},
doi = {10.1126/science.ads3972},
pmid = {41785364},
url = {https://doi.org/10.1126/science.ads3972}
}
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