ArticleActa neuropathologica communications2025
Complement pathway dysregulation and astrocyte alterations in Down syndrome: evidence from postmortem brain tissue and iPSC-derived astrocytes.
Article in Acta neuropathologica communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.STAR protocols · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundDown syndrome (DS), or trisomy 21 (T21), resulting from an extra copy of chromosome 21, occurs in 1 in 700-1,000 live births. Neuroinflammation is increasingly recognized as a critical contributor to DS neuropathology, although its underlying drivers remain unclear.
methodsIn this study, we analyzed available single-nucleus RNA sequencing (snRNAseq) data from postmortem cortical brains of individuals with DS and controls aged 36 years or younger, focusing specifically on astrocyte-enriched clusters. This analysis revealed significant alterations in complement system gene sets. To further investigate these findings, we employed a human in vitro model using astrocytes differentiated from urine-derived induced pluripotent stem cells (iPSCs) obtained from individuals with DS (T21-iPSCs). To our knowledge, this is the first study to evaluate both gene expression and protein levels of secreted complement components in T21-iPSC-derived astrocytes.
resultssnRNAseq re-analyzes identified an upregulation of complement system components, including C1R, C1S, C2, C4A, C4B, C5, C5AR1, C6, C8, CD59, CFI, and FCN2, and of glutamate transporters SLC1A3 (EAAT1/GLAST-1) and SLC1A2 (EAAT2/GLT-1) in DS astrocytes. Results from the in vitro model revealed distinct phenotypic changes in T21-iPSC-derived astrocytes, including enlarged cell and nuclear sizes, and enhanced glutamate uptake. Elevated levels of C5aR1 and MASP1 transcripts, as well as increased C4 protein secretion in culture supernatants, suggest dysregulation of the complement system in DS.
conclusionsThese findings highlight the potential contribution of astrocyte-driven complement signaling to DS neuropathogenesis. While further validation is needed, this work points to a candidate pathway that may serve as a target for future therapeutic investigation to improve the quality of life for individuals with DS.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.