Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease

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作者：Liu Xixi, Chen Chunyuan, Jiang Yaling, Wan Meidan, Jiao Bin, Liao Xinxin, Rao Shanshan, Hong Chungu, Yang Qijie, Zhu Yuan, Liu Qianqian, Luo Zhongwei, Duan Ran, Wang Yiyi, Tan Yijuan, Cao Jia, Liu Zhengzhao, Wang Zhenxing, Xie Hui, Shen Lu
期刊：International Journal of Biological Sciences
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Inadequate osteogenesis and excessive adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are key factors in the pathogenesis of osteoporosis. Patients with Alzheimer's disease (AD) have a higher incidence of osteoporosis than healthy adults, but the underlying mechanism is not clear. Here, we show that brain-derived extracellular vesicles (EVs) from adult AD or wild-type mice can cross the blood-brain barrier to reach the distal bone tissue, while only AD brain-derived EVs (AD-B-EVs) significantly promote the shift of the BMSC differentiation fate from osteogenesis to adipogenesis and induce a bone-fat imbalance. MiR-483-5p is highly enriched in AD-B-EVs, brain tissues from AD mice, and plasma-derived EVs from AD patients. This miRNA mediates the anti-osteogenic, pro-adipogenic, and pro-osteoporotic effects of AD-B-EVs by inhibiting Igf2. This study identifies the role of B-EVs as a promoter of osteoporosis in AD by transferring miR-483-5p.