Noninvasive sensory stimulation to promote glymphatic-lymphatic clearance for the treatment of Alzheimer’s Disease

阿尔茨海默病(AD)是一种无法治愈的脑部疾病，其特点是有毒物质逐渐积累 淀粉样蛋白和tau蛋白聚集体，部分原因是由于淋巴和 脑膜淋巴系统。我们最近证明了使用感官的非侵入性伽玛夹带 在伽马频率范围(30-90赫兹)内诱发神经振荡的刺激(属)可以改善 各种AD小鼠模型的病理学研究。属的小鼠表现出对小胶质细胞的积极影响， 星形胶质细胞和脑血管构筑以及减少淀粉样蛋白和过度磷酸化tau的积累 在各自的淀粉样蛋白和直肠系膜病小鼠模型中。然而，属对淋巴/淋巴的影响 系统在清除淀粉样蛋白和tau堆积方面的作用尚不清楚。我们将使用淀粉样蛋白和直肠结缔组织疗法 用小鼠模型来确定是否和识别类药物增强血管旁血管的机制 液体运动，从而促进脑膜淋巴引流和淋巴清除脑毒 代谢物，包括与淀粉样蛋白和tau有关的代谢物。

Alzheimer's disease (AD) is an incurable brain disease, distinguished by the progressive accumulation of toxic amyloid and tau protein aggregates that are partly due to impaired waste clearance by the glymphatic and meningeal lymphatic systems. We have recently shown that noninvasive Gamma ENtrainment Using Sensory stimuli (GENUS) to induce neural oscillations in the gamma frequency range (30-90 Hz) could ameliorate pathology in various AD mouse models. Mice subjected to GENUS regime exhibited positive effects on microglia, astrocytes and the brain vasculature as well as reduced accumulation of amyloid and hyperphosphorylated tau in respective amyloid and tauopathy mouse models. However, the impact of GENUS on the glymphatic/lymphatic systems in the clearance of amyloid and tau accumulation is not clear. We will use amyloid and tauopathy mouse models to determine whether and identify the mechanisms by which GENUS enhances paravascular fluid movement and thereby promotes meningeal lymphatic drainage and glymphatic clearance of brain toxic metabolites including those associated with amyloid and tau.