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

通过非侵入性感觉刺激操纵神经振荡来干预阿尔茨海默病

基本信息

批准号：
10597073
负责人：
Li-Huei Tsai
金额：
$ 71.69万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10597073
关键词：
3-Dimensional APP-PS1 Affect Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer&apos s disease risk Amyloid Area Astrocytes Auditory Brain Brain Diseases Brain region Cell Communication Cell model Cells Cerebrovascular system Coculture Techniques Cognitive Complex Data Development Disease Disease Progression Electric Stimulation Exhibits Financial cost Frequencies Functional disorder Gene Expression Genetic Risk Human Impaired cognition Inflammatory Response Intervention Mediating Memory Loss Microglia Modeling Molecular Morphology Mus Mutation Nature Nerve Degeneration Neuroimmune Neurons Outcome Pathology Pattern Phagocytes Phagocytosis Phenotype Production Publishing Response to stimulus physiology Role Sensory Signal Transduction Synapses System TREM2 gene Tauopathies Testing Therapeutic Intervention Visual Work aging population apolipoprotein E-4 behavioral outcome cell type cognitive function cognitive performance cytokine design experience experimental study genetic risk factor hyperphosphorylated tau improved induced pluripotent stem cell inflammatory modulation innovation mouse model neural neural circuit neuroinflammation neuronal excitability neuroprotection new technology pharmacologic response risk variant sensory stimulus tau Proteins tau-1 transcriptome sequencing uptake

项目摘要

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.

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。