Non-invasive modulation of meningeal lymphatics ameliorates ageing and Alzheimer’s disease-associated pathology and cognition in mice

Miao Wang, Congcong Yan, Xi Li, Tianhao Yang, Shengnan Wu, Qian Liu, Qingming Luo () and Feifan Zhou ()
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Miao Wang: School of Biomedical Engineering, Hainan University
Congcong Yan: School of Biomedical Engineering, Hainan University
Xi Li: School of Biomedical Engineering, Hainan University
Tianhao Yang: School of Biomedical Engineering, Hainan University
Shengnan Wu: School of Medical Technology, Beijing Institute of Technology
Qian Liu: School of Biomedical Engineering, Hainan University
Qingming Luo: School of Biomedical Engineering, Hainan University
Feifan Zhou: School of Biomedical Engineering, Hainan University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Meningeal lymphatic vessels (mLVs) have been shown to be involved in amyloid beta (Aβ) clearance, which is considered as a potential therapeutic target for Alzheimer’s disease (AD). In this study, based on the superficial spatial distribution of mLVs, a near-infrared light is employed to modulate lymphatic drainage, significantly improving cognition of both aged and AD (5xFAD and APP/PS1) mice, and alleviating AD-associated pathology by reducing Aβ deposition, neuroinflammation and neuronal damage. Furthermore, transmission electron microscopy imaging and RNA sequencing data indicate amelioration of mitochondrial metabolism and cellular junction of meningeal lymphatic endothelial cells (mLECs) by light modulation. These studies collectively suggest that near-infrared light treatment can improve cognitive function by strengthening scavenging ability of mLVs through restoring mLEC function. In conclusion, lymphatic drainage potentiation by light promotes pathological remission and cognitive enhancement in aging and AD mouse models, which offers a potential amelioration strategy for neurodegenerative diseases.

Date: 2024
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DOI: 10.1038/s41467-024-45656-7

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