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

阿尔茨海默病(AD)是一种无法治愈的大脑疾病，随着人类和经济成本的不断上升， 人口老龄化。其复杂的病理生理已被证明是一个令人生畏的挑战 开发有效的药理干预措施。我们最近已经证明，非侵入性伽玛 使用感觉刺激(属)在伽马频率范围内诱导神经振荡(30- 90 Hz)可改善各种AD模型小鼠的病理改变。受属制度影响的小鼠表现出 对小胶质细胞、星形胶质细胞、脑血管系统以及减少淀粉样蛋白和 淀粉样蛋白和肌萎缩侧索硬化症小鼠模型中tau蛋白的过度磷酸化。然而，这些机制通过 哪个属会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？ 安全。为此，我们将利用AD小鼠模型和创新的iPSC 3D共培养系统 评估小胶质细胞在调节类属反应中的作用，重点是小胶质细胞AD的贡献 危险基因APOE和TREM2在调节神经免疫相互作用中对属的反应。

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.