T cell infiltration mediates neurodegeneration and cognitive decline in Alzheimer's disease

Neurobiol Dis. 2024 Mar 2:106461. doi: 10.1016/j.nbd.2024.106461. Online ahead of print.ABSTRACTAlzheimer's disease (AD) is a prevalent neurodegenerative disorder with pathological features of β-amyloid (Aβ) and hyperphosphorylated tau protein accumulation in the brain, often accompanied by cognitive decline. So far, our understanding of the extent and role of adaptive immune responses in AD has been quite limited. T cells, as essential members of the adaptive immune system, exhibit quantitative and functional abnormalities in the brains of AD patients. Dysfunction of the blood-brain barrier (BBB) in AD is considered one of the factors leading to T cell infiltration. Moreover, the degree of neuronal loss in AD is correlated with the quantity of T cells. We first describe the differentiation and subset functions of peripheral T cells in AD patients and provide an overview of the key findings related to BBB dysfunction and how T cells infiltrate the brain parenchyma through the BBB. Furthermore, we emphasize the risk factors associated with AD, including Aβ, Tau protein, microglial cells, apolipoprotein E (ApoE), and neuroinflammation. We discuss their regulation of T cell activation and proliferation, as well as the connection between T cells, neurodegeneration, and cognitive decline. Understanding the innate immune response is crucial for providing comprehensive personalized therapeutic strategies for AD.PMID:38437992 | DOI:10.1016/j.nbd.2024.106461
Source: Neurobiology of Disease - Category: Neurology Authors: Source Type: research
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