Incretins GLP-1 and GIP influence Alzheimer's disease pathology and modulate key behaviors

Alzheimer's disease (AD) is a devastating neurodegenerative condition characterized by progressive cognitive decline, with increasing evidence pointing to metabolic dysfunction as a key contributor. Current treatments offer limited efficacy, primarily addressing symptoms rather than underlying pathology. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), known for their metabolic regulation, are emerging as promising therapeutic candidates due to their established neuroprotective effects and potential to address the metabolic deficits in AD. Understanding their broader impact, including on behavior, could unlock novel therapeutic strategies.

This review article systematically summarized recent advancements from both in vivo and in vitro studies investigating the therapeutic potential of incretins, specifically glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), in Alzheimer's disease (AD). The authors synthesized evidence demonstrating their neuroprotective mechanisms and explored an often-overlooked aspect: the influence of incretins on human behaviors such as eating habits, sleep patterns, physical activity, and vulnerability to substance addiction, and how these behavioral changes might contribute to neural regeneration.

Incretins, particularly GLP-1 and GIP, exert significant neuroprotective effects in Alzheimer's disease (AD) models. Studies consistently show that these peptides inhibit oxidative stress, reduce neuroinflammation, and prevent neuronal apoptosis. They also robustly improve cellular metabolic function, addressing a critical aspect of AD pathology. Beyond direct neuroprotection, the review highlighted an emerging body of evidence suggesting incretins influence various human behaviors. These include modulating eating habits, improving sleep patterns, increasing physical activity, and potentially reducing vulnerability to substance addiction. These behavioral modifications are hypothesized to indirectly support neural regeneration through various molecular mechanisms, offering a multifaceted approach to AD management. The therapeutic benefits are largely attributed to their role in enhancing energy metabolism.