Juan Young, MD, Postdoctoral Fellow in the Yale Department of Psychiatry, has been awarded a Yale Alzheimer’s Disease Research Center Pilot Project Award.
The grant will enable Young to conduct Alzheimer’s disease-related research at Yale in the coming year.
Read more about Young’s research:
Title: "Characterizing a Cytotoxic and Senescent T cell population in Alzheimer’s Disease"
Summary: Neuroinflammation has been previously linked with the pathological progression of Alzheimer’s disease (AD). However, these studies have focused primarily on the innate immune system while there remains a relative dearth of studies evaluating the potential relationships between adaptive immune functioning and the development of AD pathology. Alterations in the immune system are known to occur with aging and have been postulated to reflect an age-associated dysregulation of inflammation (i.e., inflammaging) which may have a role in AD progression. More recently, a cytotoxic and senescent CD8+ T cell population has been discovered in the CSF of patients with AD (Gates et al., 2020); a T cell population which has also been previously associated with an age-associated gene signature discovered by the Kang lab in the Section of Rheumatology, Allergy & Immunology of the Department of Internal Medicine (Park et al., 2019). Transcriptomic analysis of peripheral blood from ADRC participants similarly revealed expression of these aging genes that were associated with cytotoxic end products and pathways involved in cell cycle regulation suggesting their potential neurotoxic effects. Thus, it is postulated that this T cell population may be present in a subset of AD patients and could contribute to AD pathology. To further evaluate the biological implications of this T cell population, our lab plans to extract and analyze peripheral blood mononuclear cells (PBMCs) from the blood of AD and cognitively normal participants recruited by the Alzheimer's Disease Research Unit (ADRU). We plan to more robustly characterize these T cells by investigating effector and senescence molecules utilizing conventional flow cytometry and mass cytometery. Additionally, single cell RNA sequencing (scRNA-seq) analysis will be conducted to provide high dimensional mapping and characterization of CD4+ and CD8+ T cell heterogeneity in AD participants that would offer additional insights into the cytotoxic and senescent pathways that could contribute to AD pathology. Findings from these analyses will be correlated with measures of AD disease severity to elucidate the potential clinical implications of altered peripheral immune functioning in AD patients.