CD8+ T cells drive neuroinflammation and cognitive decline in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the world, and its pathogenesis is very complex, posing a serious threat to human health. The reciprocal regulation of the nervous and immune systems plays a key role in driving AD progression, although the specific mechanisms remain to be elucidated. In recent years, attention has increasingly focused on the role of adaptive immune cells in AD. Among them, CD8 + T cells have been found to infiltrate the brain parenchyma of AD patients, and this phenomenon is closely associated with neuronal injury and cognitive decline. This review first outlines the epidemiology and pathomechanisms of AD and systematically summarizes CD8 + T cell activation, cytotoxicity, migration, and function. It emphasizes the dual potential role of these cells in AD. These cells may exacerbate neuronal injury and cognitive dysfunction through multiple pathways, including direct cytotoxicity, release of pro-inflammatory cytokines, disruption of the blood–brain barrier, and inhibition of neuroplasticity. However, under specific microenvironmental conditions, CD8 + T cells may also exert immunomodulatory functions and confer potential protective effects. This review also discusses related therapeutic strategies based on these mechanisms. Finally, we discuss the difficulties currently facing research and future directions for clinical translation. We believe that in-depth exploration of the immunoregulatory mechanisms of CD8 + T cells in AD can provide theoretical foundations and new perspectives for developing innovative immunotherapies targeting neuroinflammation and cognitive impairment in AD.