Soluble form of receptor for advanced glycation end product receptors as novel therapeutic intervention to arrest amyloid-associated pathogenesis

Abstract

Amyloid-beta (Aβ) peptides and other amyloidogenic and inflammatory receptor for advanced glycation end product (RAGE) ligands are neutralized by soluble RAGE (sRAGE), which functions as a decoy receptor and offers a potential therapeutic intervention in neurological conditions such as Alzheimer's disease (AD). The main job of sRAGE, produced by alternative splicing or proteolytic cleavage of the full-length RAGE, is to sequester toxic ligands and stop them from interacting with cell-bound RAGE. In AD, this contact usually sets off proinflammatory and oxidative stress pathways that lead to the development of amyloid plaques, damage to neurons, and cognitive loss. By blocking these ligands, sRAGE provides neuroprotection by minimizing amyloid deposits, reducing neuroinflammation, and decreasing oxidative stress. Preclinical research has demonstrated that in animal models of AD, sRAGE dramatically lowers the amount of amyloid plaque, enhances cognitive function, and decreases inflammation. Clinical trials have shown that sRAGE can reduce patients' amyloid burden and cognitive impairment; nevertheless, there are still issues to be addressed, including patient response variability and the complex nature of neurodegeneration. Beyond AD, sRAGE has potential use in treating disorders including diabetes, atherosclerosis, and cardiovascular diseases by slowing the course of these diseases and inflammatory indicators. Even with these positive results, further study must be done to thoroughly investigate the therapeutic potential of sRAGE in various pathogenic situations, optimize dosage techniques, and customize treatment regimens. To sum up, we’ll look into this chapter on how sRAGE is a useful therapeutic tool and biomarker for treating amyloid-driven neurodegeneration and other inflammation-related disorders because it binds to amyloidogenic ligands and blocks abnormal RAGE signaling. © 2026 Elsevier Inc. All rights reserved..