Unraveling APOE4: The dual role in CNS and peripheral inflammation in Alzheimer's disease.

Inflammation in both CNS and peripheral circulation system is known to have a significant impact in AD pathogenesis. In the CNS, AD-related inflammation involves the activation of various types of immune cells, such as microglia, astrocytes, and T cells. Meanwhile, one of the hallmarks of peripheral circulation inflammation in AD is activation of T cells. In addition, Apolipoprotein E4 (APOE4), as a key genetic risk factor for late-onset AD, significantly influences both CNS and peripheral circulation system inflammation in the pathogenesis of AD. Moreover, APOE4 play a key role in various pathological changes in AD, such as Aβ accumulation, tau phosphorylation, lipid metabolism disorders, and BBB dysfunction, resulting in microglia, astrocytes, and T cells activation, as well as the release of inflammatory factors. This comprehensive review aims to elucidate the specific mechanisms through which APOE4 triggers inflammation in both CNS and peripheral circulation system in the context of AD. Furthermore, we also summarize several therapeutic approaches that target APOE for the treatment of AD.