Impact of T cells on the CNS during aging and Alzheimer’s disease

PROJECT NARRATIVE In humans, risk factors for Alzheimer’s disease (AD) include aging and genetic risk factors implicated in altering brain inflammation and microglia, the resident immune cell of the brain, suggesting that factors that shape these responses can alter pathology. We have shown that CD8+ T cells increase in the CNS during the process of tauopathy or age-associated amyloidosis, lending evidence to an emerging idea that peripheral adaptive immune cells (i.e. CD4+T cells, CD8+ T cells, B cells) may also play a role in shaping central nervous system (CNS) pathology and microglial function. The goal of this proposal is to determine how CD8+ T cells impact cognition, neuroinflammation, gliosis, microglial transcriptomes and pathology observed during the process of age-associated amyloidosis or tauopathy, the two hallmark pathological features of AD, and define the transcriptomic profiles of CNS CD8+ T cells.