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

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

doi:10.7150/ijbs.79461

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Int J Biol Sci 2023; 19(8):2409-2427. doi:10.7150/ijbs.79461 This issue Cite

Research Paper

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

Xixi Liu^1#, Chunyuan Chen^2#, Yaling Jiang¹, Meidan Wan¹, Bin Jiao^1,3,4,5,6, Xinxin Liao^3,4,5,6, Shanshan Rao², Chungu Hong², Qijie Yang¹, Yuan Zhu¹, Qianqian Liu¹, Zhongwei Luo², Ran Duan², Yiyi Wang², Yijuan Tan², Jia Cao², Zhengzhao Liu^2,3,7, Zhenxing Wang^2✉, Hui Xie^2,3,7✉, Lu Shen^1,3,4,5,6✉

1. Department of Neurology, Xiangya Hospital, Central South University, 410008 Changsha, Hunan, China.
2. Department of Orthopedics, Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, 410008 Changsha, Hunan, China.
3. National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), 410008 Changsha, Hunan, China.
4. Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, 410008 Changsha, Hunan, China.
5. Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, 410008 Changsha, Hunan, China.
6. Key Laboratory of Hunan Province in Neurodegenerative Disorders, 410008 Changsha, Hunan, China.
7. Department of Sports Medicine, Xiangya Hospital, Central South University, 410008 Changsha, Hunan, China.
# Xixi Liu and Chunyuan Chen contributed equally to this work.

Citation:

Liu X, Chen C, Jiang Y, Wan M, Jiao B, Liao X, Rao S, Hong C, Yang Q, Zhu Y, Liu Q, Luo Z, Duan R, Wang Y, Tan Y, Cao J, Liu Z, Wang Z, Xie H, Shen L. Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease. Int J Biol Sci 2023; 19(8):2409-2427. doi:10.7150/ijbs.79461. https://www.ijbs.com/v19p2409.htm

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Abstract

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.

Keywords: Alzheimer's disease, extracellular vesicles, osteoporosis, miR-483-5p, adipogenesis

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APA

Liu, X., Chen, C., Jiang, Y., Wan, M., Jiao, B., Liao, X., Rao, S., Hong, C., Yang, Q., Zhu, Y., Liu, Q., Luo, Z., Duan, R., Wang, Y., Tan, Y., Cao, J., Liu, Z., Wang, Z., Xie, H., Shen, L. (2023). Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease. International Journal of Biological Sciences, 19(8), 2409-2427. https://doi.org/10.7150/ijbs.79461.

ACS

Liu, X.; Chen, C.; Jiang, Y.; Wan, M.; Jiao, B.; Liao, X.; Rao, S.; Hong, C.; Yang, Q.; Zhu, Y.; Liu, Q.; Luo, Z.; Duan, R.; Wang, Y.; Tan, Y.; Cao, J.; Liu, Z.; Wang, Z.; Xie, H.; Shen, L. Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease. Int. J. Biol. Sci. 2023, 19 (8), 2409-2427. DOI: 10.7150/ijbs.79461.

NLM

CSE

Liu X, Chen C, Jiang Y, Wan M, Jiao B, Liao X, Rao S, Hong C, Yang Q, Zhu Y, Liu Q, Luo Z, Duan R, Wang Y, Tan Y, Cao J, Liu Z, Wang Z, Xie H, Shen L. 2023. Brain-derived extracellular vesicles promote bone-fat imbalance in Alzheimer's disease. Int J Biol Sci. 19(8):2409-2427.

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