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：
10378329
负责人：
Li-Huei Tsai
金额：
$ 72.9万
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/10378329
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 Pharmacology Phenotype Production Publishing Response to stimulus physiology Role Sensory Signal Transduction Synapses System TREM2 gene Tauopathies Testing Therapeutic Intervention Visual Work aging population base 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 circuit neuroinflammation neuronal excitability new technology relating to nervous system response risk variant sensory stimulus tau Proteins tau phosphorylation 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.

阿尔茨海默氏病 (AD) 是一种无法治愈的脑部疾病，其造成的人力和财力成本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。我们最近证明了非侵入性伽玛 ENtrainment 使用感觉刺激 (GENUS) 诱导伽马频率范围 (30- 90 Hz）可以改善各种 AD 小鼠模型的病理学。受到 GENUS 制度影响的小鼠表现出对小胶质细胞、星形胶质细胞、脑血管系统产生积极影响，并减少淀粉样蛋白和淀粉样蛋白的积累淀粉样蛋白和 tau 病小鼠模型中过度磷酸化的 tau 蛋白。然而，该机制通过其中 GENUS 影响细胞间相互作用，特别是神经元和小胶质细胞之间的相互作用，但不清除。为此，我们将结合使用 AD 小鼠模型和创新的 iPSC 3D 共培养系统评估小胶质细胞在改变 GENUS 反应中的作用，重点关注小胶质细胞 AD 的贡献风险基因 APOE 和 TREM2，调节响应 GENUS 的神经免疫相互作用。