Innate and adaptive glial cell responses in Alzheimer’s disease

Abstract

Alzheimer’s disease (AD), which affects around twenty-seven million people globally, is an aging-related neurodegenerative condition characterized by the extracellular deposition of misfolded amyloid-β (Aβ) peptides and the intracellular production of neurofibrillary tangles (NFTs) AD results from the death of certain groups of neurons in the brain while appearing to have no impact on neighboring neurons. It is progressive and incurable. Therefore, the pathophysiology of afflicted populations and the development of intervention measures to stop neuronal cell death have been the main areas of attention for delineating therapeutic options. Proinflammatory cytokines are responsible for the stimulation of inflammatory responses and are mostly generated by activated macrophages in the brain. This review discusses how glial cells and innate and adaptive immune responses have a critical role in AD. It also provides information about microglial activation through the cluster of differentiation 40 (CD40) ligation and CD40L. CD40L ligation of microglial CD40 results in a large increase in tumor necrosis factor-α (TNF-α) production. Cultured cortical neuronal injury is caused when microglia are activated by CD40 ligation in the presence of interferon-γ (IFN-γ). This injury is significantly reduced by blocking the CD40 pathway or neutralising TNF-α. The management of AD would require integrating all available information about the innate and adaptive immune response affecting AD-related neuronal death.