biostudies-literatureAli MFonds National de la Recherche LuxembourgFonds National de la Recherche Luxembourg (National Research Fund)119https://www.ebi.ac.uk/biostudies/studies/S-EPMC10920792biostudies-literatureUnknown10(1)Alzheimer's disease (AD) progression and pathology show pronounced sex differences, but the factors driving these remain poorly understood. To gain insights into early AD-associated molecular changes and their sex dependency for tau pathology in the cortex, we performed single-cell RNA-seq in the THY-Tau22 AD mouse model. By examining cell type-specific and cell type-agnostic AD-related gene activity changes and their sex-dimorphism for individual genes, pathways and cellular sub-networks, we identified both statistically significant alterations and interpreted the upstream mechanisms controlling them. Our results confirm several significant sex-dependent alterations in gene activity in the THY-Tau22 model mice compared to controls, with more pronounced alterations in females. Both changesCell death discoverySingle cell transcriptome analysis of the THY-Tau22 mouse model of Alzheimer's disease reveals sex-dependent dysregulations.PMC10920792INTER/22/17104370ERAPERMED 2020-314Buee LSciortino ASkupin AGlaab EHeurtaux TAli MCoowar DBlum DGarcia PButtini MGrzyb KLunkes LPThomas MHalder RfalseSingle cell transcriptome analysis of the THY-Tau22 mouse model of Alzheimer's disease reveals sex-dependent dysregulations.Alzheimer's disease (AD) progression and pathology show pronounced sex differences, but the factors driving these remain poorly understood. To gain insights into early AD-associated molecular changes and their sex dependency for tau pathology in the cortex, we performed single-cell RNA-seq in the THY-Tau22 AD mouse model. By examining cell type-specific and cell type-agnostic AD-related gene activity changes and their sex-dimorphism for individual genes, pathways and cellular sub-networks, we identified both statistically significant alterations and interpreted the upstream mechanisms controlling them. Our results confirm several significant sex-dependent alterations in gene activity in the THY-Tau22 model mice compared to controls, with more pronounced alterations in females. Both changes2024-01-01T00:00:00Z2024 Mar2026-07-15T13:50:26.67Z2026-07-05T03:11:21.159ZS-EPMC109207923845389410.1038/s41420-024-01885-9