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

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. Comparative gene expression profiling analysis of RNA-seq data for hippocampus, meninges and meningeal lymphatic endothelial cells of 6-month 5xFAD male mice receiving light treatment vs. no-light treatment, as well as 6-month 5xFAD male mice vs. 6-month wild type mice.

脑膜淋巴管（Meningeal lymphatic vessels, mLVs）已被证实参与β淀粉样蛋白（amyloid beta, Aβ）的清除过程，该过程被视为阿尔茨海默病（Alzheimer’s disease, AD）的潜在治疗靶点。本研究基于脑膜淋巴管的浅表空间分布特征，采用近红外光调节淋巴引流，可显著改善老年小鼠以及AD模型（5xFAD与APP/PS1）小鼠的认知功能，并通过减少β淀粉样蛋白沉积、神经炎症与神经元损伤，缓解阿尔茨海默病相关病理改变。此外，透射电子显微镜成像与RNA测序（RNA sequencing, RNA-seq）数据显示，光调节可改善脑膜淋巴管内皮细胞（meningeal lymphatic endothelial cells, mLECs）的线粒体代谢与细胞连接功能。上述研究共同表明，近红外光治疗可通过恢复脑膜淋巴管内皮细胞功能，增强脑膜淋巴管的清除能力，进而改善认知功能。综上，通过光调控增强淋巴引流，可促进衰老与阿尔茨海默病小鼠模型的病理缓解与认知功能提升，为神经退行性疾病提供了潜在的改善策略。本数据集包含对6月龄雄性5xFAD小鼠（接受光治疗vs. 未接受光治疗）以及6月龄雄性5xFAD小鼠与6月龄野生型小鼠的海马体、脑膜、脑膜淋巴管内皮细胞的RNA测序数据进行的比较基因表达谱分析。