| Experiment Id | GSE254970 | Name | Age, Sex and Alzheimers disease: a longitudinal study of 3xTg-AD mice reveals sex-specific disease trajectories and inflammatory responses mirrored in postmortem brains from Alzheimers patients |
| Experiment Type | RNA-Seq | Study Type | Baseline |
| Source | GEO | Curation Date | 2024-07-15 |
| description | Aging and sex are major risk factors for developing late-onset Alzheimers disease. Compared to men, women are not only nearly twice as likely to develop Alzheimers, but they also experience worse neuropathological burden and cognitive decline despite living longer with the disease. It remains unclear how and when sex differences in biological aging emerge and contribute to Alzheimers disease pathogenesis. We hypothesized that these differences lead to distinct molecular Alzheimers disease signatures in males and females, which could be harnessed for therapeutic and biomarker development. We aged male and female, 3xTg-AD and B6129 control mice across their respective lifespans while longitudinally collecting brain samples. We conducted RNA sequencing analysis on bulk brain tissue and examined differentially expressed genes between 3xTg-AD and B6129 samples and across ages in each sex. 3xTg-AD males experienced an accelerated upregulation of immune-related gene expression in the brain relative to females, especially in genes involved in complement system activation, suggesting distinct inflammatory disease trajectories between the sexes. Our data demonstrate that chronic inflammation and complement activation are associated with increased mortality, revealing that age-related changes in immune response act as a primary driver of sex differences in Alzheimers disease trajectories. To examine molecular changes throughout disease progression, we collected brain tissue from male and female, 3xTg-AD and B6129 control mice, between the ages of 6- and 24-months-old. |
