Mechanistic Insights and Emerging Therapeutic Targets of Alzheimer's Disease: From the Perspective of Inter-Organ Crosstalk.

Abstract

With complex pathogenesis, Alzheimer's disease (AD) is a neurological illness that has worsened over time. Inter-organ crosstalk, which is essential for coordinating organ function and maintaining homeostasis, is involved in multiple physiological and pathological events. Increasing evidence suggests that AD is closely associated with multiple diseases of peripheral organs, including the gut, adipose tissue, liver, and bone. Despite numerous studies on AD, the ambiguous role of pathological peripheral organ-brain crosstalk in the development of AD remains incompletely understood, and the potential mechanisms remain obscure. This review summarizes the current knowledge of the relationship between AD and disorders of various organs from clinical and preclinical evidence. Additionally, we elucidate the mechanisms underlying AD development from the perspective of "organ-organ crosstalk", including the gut-brain, adipose tissue-brain, liver-brain and bone-brain axes. On the basis of the peripheral organ-brain crosstalk, we emphasize promising therapeutic targets with the hope of providing novel perspectives for AD management.