To Elucidate the Role of Memory T Cells as a Determinant of Age-Related Inflammation in Alzheimer’s Disease

Alzheimer’s disease (AD) is an irreversible, progressive and fatal brain disease with complex etiology likely dominated by the accumulation of environmental insults. As the brain ages, it becomes more inflamed, which is thought to exacerbate AD—but the underlying causes of this increased age-related inflammation are unknown. We hypothesize that one’s prior history of pathogen infections may be a major contributor to developing chronic inflammation in the brain and increasing AD risk. Over time, infections we experience change types of immune cells and chemicals in the brain, even changing how the brain cells function. We postulate the accumulation of memory T cells in brain, which develop in response to repeated infections to remember the pathogen when encountered again, drive inflammation and neuronal degeneration. The caveat is most research conducted on AD in mice is performed in very clean conditions, and the mice never get sick from common germs. Therefore, these mice lack memory T cells in their brains that humans all have from experiencing infections. Therefore, to generate better, more physiological AD mouse models that recapitulate environmental conditions outside the confines and sterility of a research laboratory, we will infect mice that already are prone to developing AD with different pathogens throughout their life. We will then study whether the accumulation of T cells in the brain affects it, and we will also search for early signs of AD and memory problems. Ultimately, these studies will enable us to determine whether a history of infections makes AD and brain problems worse as we age.