Role of incretins in Alzheimer’s disease and their impact on behavioral aspects

ABSTRACT: Recent studies highlight the therapeutic potential of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), two key incretin components, in neurodegenerative diseases, particularly Alzheimer's disease (AD). Although the incretin pathway may also affect other neurodegenerative conditions, this discussion focuses on AD. The therapeutic benefits are largely attributed to their role in enhancing energy metabolism. In vivo and in vitro studies have demonstrated that GLP-1 and GIP exert neuroprotective effects through the inhibition of oxidative stress, neuroinflammation, and neuronal apoptosis, while improving cellular metabolic function. Additionally, an emerging but often overlooked body of evidence suggests that incretin may influence human behaviors, such as eating habits, sleep patterns, physical activity, and vulnerability to substance addiction. These behavioral changes could, in turn, support neural regeneration through various molecular mechanisms. This article summarizes recent advancements in the understanding of incretin's influence on human behavior and its implications for AD.