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

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

Volume: 18 Issue: 3

Author(s): Shima Mehrabadi*

Affiliation:

• Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

Keywords: Alzheimer's disease, PD-L1, PD-1, immune checkpoint, neuroinflammation, microglia, amyloid-β, phagocytosis, therapeutic target.

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.

Cite this article as:

Mehrabadi Shima*, The Therapeutic Potential of Targeting the Pd-L1/Pd-1 Immune Checkpoint Pathway in Alzheimer's Disease, Current Aging Science 2025; 18 (3) . https://dx.doi.org/10.2174/0118746098342537241121042621