Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives

Abstract Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD. We review the effects of AD on bone from the aspects of AD pathogenic proteins, AD risk genes, neurohormones, neuropeptides, neurotransmitters, brain‐derived extracellular vesicles (EVs), and the autonomic nervous system. Correspondingly, we elucidate the underlying mechanisms of the involvement of bone in the pathogenesis of AD, including bone‐derived hormones, bone marrow‐derived cells, bone‐derived EVs, and inflammation. On the basis of the crosstalk between bone and the brain, we propose potential strategies for the management of AD with the hope of offering novel perspectives on its prevention and treatment. Highlights The pathogenesis of AD, along with its consequent changes in the brain, may involve disturbing bone homeostasis. Degenerative bone disorders may influence the progression of AD through a series of pathophysiological mechanisms. Therefore, relevant bone intervention strategies may be beneficial for the comprehensive management of AD.