Project description:This project aims to assess the transcriptomic signature in the dorsal hippocampus of 12 month-old Thy-Tau22 mice in basal conditions and treated with the vehicle CSP (n=4) or CSPTTK21 (n=3), compared to CSP-treated WT (n=4) mice.
Project description:This project aims to identify epigenetic signatures (histone acetylation-related) associated with Tau pathology in hippocampal region of Thy-Tau22 mice in basal conditions and after treatment with CSP-TTK21. For this we performed ChIP for H3K27ac in whole hippocampus of 12 month-old Tau reated with the vehicle CSP or CSP-TTK21, as well as of CSP-treated 12 month-old WT mice.In total we have 6 IPed samples (Biological duplicates were analyzed) and 3 Inputs. Spike-in from drosophila chromatin was added to the samples.
Project description:Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta and tau proteins in vulnerable brain regions. While the main pathological hallmarks of AD are shared across the sexes, a diverse array of sex differences have been documented for both AD-associated symptoms and molecular characteristics. To gain insights into AD-associated molecular changes and their sex-dependence for tau pathology in the cortex as one of the most severely affected brain regions, we performed single-cell gene activity profiling for the THY-Tau22 mouse model. By studying cell-type specific and cell-type agnostic AD-related changes and their sex-dimorphism for single genes, pathways and cellular sub-networks, we aimed to identify both statistically significant alterations and interpret the upstream mechanisms that control them.
Project description:Alzheimer's disease (AD) displays sex-specific differences in prevalence and progression, but the underlying molecular mechanisms remain unclear. To investigate sex-dependent molecular changes associated with tau pathology at a late disease stage, we performed single-cell RNA sequencing on cortical tissue from 17-month-old THY-Tau22 mice and wildtype littermates of both sexes. The analysis revealed extensive sex-specific and sex-dimorphic transcriptomic alterations across multiple cell types, with particularly pronounced changes in microglia and oligodendrocytes. Key pathways affected in a sex-dependent manner included RNA processing and splicing, stress response pathways, neurotransmitter signaling, and protein degradation pathways. Network analysis identified the genes Clu, Mbp, Fos and Junb as potential regulatory hubs. Multiple genes with established implications in AD, including the long non-coding RNA gene MALAT1, showed concordant sex-specific changes when compared with both earlier time points and human AD data. This study provides a comprehensive characterization of sex-dependent transcriptomic changes in late-stage tau pathology, revealing new insights into the interplay between AD-like pathology and biological sex.
