Manipulating Neural Oscillations with Non-Invasive Sensory Stimulation for Alzheimer's Disease Intervention

阿尔茨海默氏病（AD）是一种无法治愈的脑部疾病，随着人类和经济成本的不断上升， 人口老龄化其病理生理学的复杂性已被证明是一个艰巨的挑战， 开发有效的药物干预措施。我们最近的研究表明， 使用感觉刺激（GENUS）诱导伽马频率范围（30- 40 Hz）的神经振荡 90 Hz）可以改善各种AD小鼠模型的病理学。接受GENUS方案的小鼠表现出 对小胶质细胞、星形胶质细胞、脑血管系统的积极作用，以及减少淀粉样蛋白和 在相应的淀粉样蛋白和tau蛋白病小鼠模型中过度磷酸化的tau。然而， 哪些GENUS影响细胞间的相互作用，特别是神经元和小胶质细胞之间的相互作用， 清楚为此，我们将结合AD小鼠模型和创新的iPSC 3D共培养系统 评估小胶质细胞在改变GENUS反应中的作用，重点是小胶质细胞AD的贡献 风险基因，APOE和TREM 2，在调节响应GENUS的神经免疫相互作用。

Alzheimer's disease (AD) is an incurable brain disorder, with a staggering human and financial cost in a rising aging population. The complexity of its pathophysiology has proven to be a daunting challenge in the development of effective pharmacological interventions. 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, cerebral vasculature, as well as reduced accumulation of amyloid and hyperphosphorylated tau in respective amyloid and tauopathy mouse models. However, the mechanisms by which GENUS impacts cell-cell interactions, in particular, interactions between neurons and microglia, are not clear. To this end, we will utilize a combination of AD mouse models and innovative iPSC 3D co-culture system to assess the role of microglia in modifying the GENUS response, focusing on the contributions of microglial AD risk genes, APOE and TREM2, in modulating the neuroimmune interactions in response to GENUS.