Alzheimer’s disease: The role of T lymphocytes in neuroinflammation and neurodegeneration

Abstract

Alzheimer’s disease, the leading cause of progressive cognitive decline globally, has been reported to be enhanced by neuroinflammation. Brain-resident innate immune cells and adaptive immune cells work together to produce neuroinflammation. Studies over the past decade have established the neuroimmune axis present in Alzheimer’s disease; the crosstalk between adaptive and innate immune cells within and outside the brain is crucial to the onset and progression of Alzheimer’s disease. Although the role of the adaptive immune system in Alzheimer's disease is not fully understood, it has been hypothesized that the brain's immune homeostasis is significantly disrupted, which greatly contributes to neuroinflammation. Brain-infiltrating T cells possess proinflammatory phenotypes and activities that directly contribute to neuroinflammation. The pro-inflammatory activities of the adaptive immune system in Alzheimer’s disease are characterized by the upregulation of effector T cell activities and the downregulation of regulatory T cell activities in the brain, blood, and cerebrospinal fluid. In this review, we discuss the major impact of T lymphocytes on the pathogenesis and progression of Alzheimer’s disease. Understanding the role and mechanism of action of T cells in Alzheimer’s disease would significantly contribute to the identification of novel biomarkers for diagnosing and monitoring the progression of the disease. This knowledge could also be crucial to the development of immunotherapies for Alzheimer’s disease.