The Therapeutic Potential of Targeting the Pd-L1/Pd-1 Immune Checkpoint Pathway in Alzheimer's Disease

Abstract

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β plaques, neurofibrillary tangles, and chronic neuroinflammation. Emerging evidence suggests that the PD-L1/PD-1 immune checkpoint pathway plays a critical role in modulating neuroinflammation, microglial function, and amyloid-β clearance in AD. This review summarizes the current understanding of the PD-L1/PD-1 pathway in AD and discusses its potential as a therapeutic target. Preclinical studies and clinical trials have demonstrated that targeting the 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 existing immunotherapy 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 or amyloid-β-targeting treatments. This review provides a comprehensive and up-to-date analysis of the PD-L1/PD-1 immune checkpoint pathway's role in Alzheimer's disease, highlighting its promising therapeutic potential for improving patient outcomes. Further research is warranted to optimize treatment strategies and evaluate the long-term safety and efficacy of targeting this axis in clinical settings.