The analysis of our datasets from 3xTg-AD and WT mice are consistent with these data and unbiased cell fate trajectory analysis clearly showed that brain CD8+ T cell differentiation occurred on a tightly organized trajectory starting from a common root and ending with two differentiation states distinguished by the expression of Itgae and Eomes. However, only CD103– (not CD103+) CD8+ Trm cells infiltrating the brains of 3xTg-AD mice were strongly associated with the “Alzheimer’s disease” pathway, suggesting these cells have distinct pathological functions specifically promoting AD. Here, CD8A is linked to Alzheimer disease.