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

• 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
• 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' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' 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

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）是一种无法治愈的脑部疾病，其造成的人力和经济成本不断上升，令人震惊