Targeting the crosstalk between Alzheimer’s disease and gastrointestinal cancers

Epidemiological studies have revealed an inverse association between Alzheimer's disease and cancer. Here, we discuss the mechanisms involved in the relationship between Alzheimer's disease and gastrointestinal cancers, particularly pancreatic and gastric-colorectal cancers. The gut‒brain axis and pancreas‒brain axis connect the central nervous system with peripheral organs and form immune‒metabolic networks. We focus on bidirectional tumor-brain communication, involving cell-death pathways, apoptosis, metabolic dysregulation, microbiota, metabolic dysregulation, neuroinflammation, immune system and sensory-sympathetic circuits, and neural remodeling. Furthermore, we discuss potential integrated, multitarget therapeutic strategies, including metabolic regulation, microbiome interventions, and immune modulation. Prospective longitudinal cohorts incorporating prediagnostic exposures and molecular pathology are needed to establish temporality.