Complement pathway dysregulation and astrocyte alterations in Down syndrome: evidence from postmortem brain tissue and iPSC-derived astrocytes.

ABSTRACT:

Background

Down 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.

Methods

In 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

SUBMITTER: Teles E Silva AL 

PROVIDER: S-EPMC12797606 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature