Age-associated CD8+ T cells accumulate in the aging brain and dementia 2496

Abstract Description Introduction By 2050, individuals over 65 will outnumber those under 65 in the U.S., increasing neurodegenerative diseases like Alzheimer’s and vascular dementia. Dementia cases have risen by 20% over 20 years and are expected to triple by 2050 due to aging. Aging impairs cerebrovascular function, leading to vascular stiffness and blood-brain barrier (BBB) disruption, which allows immune cell infiltration associated with neuroinflammation, cognitive decline, and dementia progression. Hypothesis: How do Age-Associated CD8+ T cells (TAA cells) contribute to neuroinflammation and dementia? What gene signature and mechanism characterize cytotoxic CD8+ T cells in aging? Goals: To identify accumulation patterns and transcriptomic differences of TAA cells in aging and to explore the role of Gzmk+ effector memory CD8+ T cells in age-related inflammation. Methods Using single-cell RNA sequencing in a vascular stenosis mouse model for vascular dementia, we compared brain samples of 21-month-old and 3-month-old mice, identifying and characterizing Gzmk+ effector memory CD8+ T cells in aging. Results Gzmk+ effector memory CD8+ T cells increased in 21-month-old mice, with unique transcriptomic and cytokine profiles. Conclusions These findings highlight the role of TAA cells in age-related inflammation and dementia, underscoring the value of aged animal models for studying chronic inflammatory diseases and guiding therapeutic strategies. Funding Sources This work was supported by the National Institutes of Health/National Institute on Aging Grant R00 AG068309 (to D.J.T.); Nathan Shock Center, which is supported by the National Institutes of Health/National Institute on Aging Grant P30 AG050886; and by the Glenn Foundation for Medical Research and American Federation for Aging Research Junior Faculty Award A24063 (to D.J.T.). Topic Categories Neuroimmunology (NEUR)