Characterizing the Role of T Cells in Alzheimer’s Disease

Science Center, Bent Corridor

Alzheimer’s Disease (AD) is the 6th leading cause of death in the U.S., affecting 5 million Americans. Previous research has utilized an aggressive model of AD, the 5XFAD mouse, and crossed it with mice that do not have T or B cells, key players of the immune system. This cross was found to have twice the amount of plaque burdens and increased inflammation in the brain when compared to 5XFAD mice with an intact immune system. The Mariani lab has focused on one part of the immune system, crossing 5XFAD mice with mice lacking the main types of T cells (TCR αβ KO mice) to characterize the role of T cells in Alzheimer’s disease. Behavioral testing did not have statistically significant results, most likely due to early observation in disease progression and a relatively small number of mice observed (n=1-4). Flow cytometry performed on post-mortem spleens has shown that all mice (Wild Type Control, WT/TCR, and 5XFAD/TCR) have relatively similar levels of CD3, CD8, and CD4, T cells. This indicates that having only one copy of the TCR mutation is not sufficient to create dramatic loss of T cells. Therefore, new 5XFAD mice will be bred to have either one or two copies of TCR αβ KO, which will result in TCR/TCR mice having no T cells, allowing us to accurately model the effect of T cells on Alzheimer’s Disease progression. Further behavioral testing, flow cytometry, and tissue staining will be performed on this new cohort of mice.