The Therapeutic Potential of Targeting the Pd-L1/Pd-1 ImmuneCheckpoint Pathway in Alzheimer's Disease
Shima Mehrabadi · Current Aging Science · 2024
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized bythe accumulation of amyloid-β plaques, neurofibrillary tangles, and chronic neuroinflammation.Emerging evidence suggests that the PD-L1/PD-1 immune checkpoint pathway plays a criticalrole in modulating neuroinflammation, microglial function, and amyloid-β clearance in AD. Thisreview summarizes the current understanding of the PD-L1/PD-1 pathway in AD and discusses itspotential as a therapeutic target. Preclinical studies and clinical trials have demonstrated that targetingthe PD-L1/PD-1 axis can enhance microglial phagocytosis, promote amyloid-β clearance,and reduce neuroinflammation. We examine the potential benefits and challenges of using existingimmunotherapy drugs, such as anti-PD-L1 and anti-PD-1 antibodies, in the context of AD.Additionally, we explore the development of novel, more specific agents targeting the PDL1/PD-1 pathway, as well as potential synergistic approaches with other immunomodulatory oramyloid-β-targeting treatments. This review provides a comprehensive and up-to-date analysis ofthe PD-L1/PD-1 immune checkpoint pathway's role in Alzheimer's disease, highlighting itspromising therapeutic potential for improving patient outcomes. Further research is warranted tooptimize treatment strategies and evaluate the long-term safety and efficacy of targeting this axisin clinical settings.