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，其特征在于毒性物质的进行性积累。 淀粉样蛋白和tau蛋白聚集体，部分是由于受损的废物清除胶质淋巴和 脑膜淋巴系统我们最近表明，使用感官的非侵入性伽马夹带 在伽马频率范围（30-90 Hz）内诱导神经振荡的刺激（GENUS）可以改善 在各种AD小鼠模型中的病理学。接受GENUS方案的小鼠对小胶质细胞表现出积极作用， 星形胶质细胞和脑血管系统以及淀粉样蛋白和过度磷酸化tau蛋白的积累减少 在各自的淀粉样蛋白和tau蛋白病小鼠模型中。然而，GENUS对胶质淋巴/淋巴细胞的影响 淀粉样蛋白和tau积聚的清除系统尚不清楚。我们将使用淀粉样蛋白和tau蛋白 小鼠模型，以确定是否和确定GENUS增强血管旁 液体运动，从而促进脑膜淋巴引流和胶质淋巴清除脑毒性 代谢物，包括与淀粉样蛋白和tau蛋白相关的代谢物。

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.