Single cell transcriptome analysis of the THY-Tau22 mouse model of Alzheimer's disease reveals sex-dependent dysregulations

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. The study used the THY-Tau22 transgenic mouse model of Alzheimer's disease, which overexpresses a mutant human tau protein. Single-cell RNA-seq was performed on brain cortex samples from 7-month old THY-Tau22 mice and wildtype control mice (5 mice per genotype and sex). The experimental conditions compared were: THY-Tau22 transgenic males (n=5), Wildtype control males (n=5), THY-Tau22 transgenic females (n=5), and Wildtype control females (n=5).