{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304499/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304499"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Unique transcriptomic alterations in 5XFAD;PS19 mouse model align with human Alzheimer's disease","description":"Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) plaques and tau tangles, yet their combined effects on brain cell types remain poorly understood. To investigate this, we generated a dual-pathology mouse model (5XFAD;PS19) and performed single-nucleus RNA sequencing (snRNA-seq), integrating findings with human AD datasets. We uncovered widespread, synergistic transcriptional disruptions not seen in single-pathology models, including changes in gene co-expression networks and cell type-specific gene expression. Notably, we observed coordinated transcriptomic alterations involving both microglia and oligodendrocytes, particularly in immune-related pathways and suppression of synaptic transmission. The combined model significantly overlapped with human AD transcriptomic profiles at both gene and pathway levels, highlighting its translational relevance. This well-powered, sex-balanced study dissects the synergistic effects of Aβ and tau across multiple brain cell types. Our findings support the importance of modeling combined-pathology to uncover potential pharmacological targets for therapeutic development.","dates":{"publication":"2026/08/11"},"accession":"GSE304499","cross_references":{"GSM":["GSM9151569","GSM9151568","GSM9151567","GSM9151566","GSM9151559","GSM9151561","GSM9151572","GSM9151571","GSM9151560","GSM9151570","GSM9151565","GSM9151564","GSM9151563","GSM9151574","GSM9151562","GSM9151573"],"GPL":["24247"],"GSE":["304499"],"taxon":["Mus musculus"],"PMID":["[42576162]"]}}