Neuroinflammation as a core pathogenic mechanism of Alzheimer’s disease: recent research advances and related therapeutical approaches

Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) accumulation, tau deposition, oxidative stress, and neuroinflammation. However, recent research focused more on neuroinflammation and oxidative stress than protein deposits, as the therapeutical effect against the latter has been relatively disappointing over the years. Since then, many novel findings have emerged, indicating neuroinflammation as another crucial contributor in AD pathogenesis rather than a secondary effect of protein deposition, and shed some light on the therapeutical design for AD. This paper will discuss some new understanding of neuroinflammation in AD. Unlike what is previously known as an immune-privileged site, the brain has a solid immune response upon detecting foreign pathogens and protein deposits, mediated mainly by glial cells. This immune response then ends with chronic neuroinflammation, which accelerates AD progression. Thus, this paper will highlight the role of glial cells in neuroinflammation and bring up the usually neglected contribution of periphery immune system and microbiomes infection as well, together depict a broader picture of neuroinflammation in the pathogenesis of AD, along with potential therapeutical advance with an emphasis on immunotherapy.