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Noninvasive sensory stimulation to promote glymphatic-lymphatic clearance for the treatment of Alzheimer’s Disease

无创感觉刺激促进类淋巴清除，治疗阿尔茨海默病

基本信息

批准号：
10612021
负责人：
Li-Huei Tsai
金额：
$ 62.18万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-15 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10612021
关键词：
Ablation Acceleration Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Amyloid Amyloid Proteins Anesthetics Astrocytes Attenuated Automobile Driving Blood Vessels Brain Brain Diseases Carotid Stenosis Cells Cerebrospinal Fluid Cerebrovascular system Chronic Complementary Health Coupled Dextrans Diameter Disease Drainage procedure Endothelial Cells Excision Exhibits Extravasation Fluorescence Microscopy Fluorescence-Activated Cell Sorting Frequencies Gap Junctions Genetic Transcription Healthcare Impaired cognition Impairment Integrative Medicine Intercellular Fluid Laser injury Light Liquid substance Literature Lymphatic Diseases Lymphatic System Lymphatic clearance Lymphatic function Maps Mediating Meningeal Meningeal lymphatic system Meninges Metabolic Microglia Microscopy Molecular Monitor Morphology Movement Mus Music Therapy Neurons Nitric Oxide Optics Pathogenicity Pathology Pathway interactions Pattern Pericytes Physical Exercise Physiological Play Population Potassium Process Proteins Regimen Role Sensory Signal Transduction Sleep Smooth Muscle Myocytes System Tauopathies Testing Tracer Vasoactive Intestinal Peptide aquaporin 4 awake brain parenchyma cisterna magna cognitive function dietary supplements fitness glymphatic clearance glymphatic dysfunction glymphatic flow glymphatic system hyperphosphorylated tau immunoregulation improved in vivo insight loss of function lymph flow lymphatic drainage lymphatic vessel mindfulness mouse model neural neurotoxic neurovascular neurovascular coupling neurovascular unit novel therapeutic intervention pharmacologic programs protein aggregation recruit response sensory stimulus single-cell RNA sequencing solute sound tau Proteins tau aggregation two-photon vasomotion wasting water channel

项目摘要

Alzheimer's disease (AD) is an incurable brain disease, distinguished by the progressive accumulation of toxic amyloid and tau protein aggregates that are partly due to impaired waste clearance by the glymphatic and meningeal lymphatic systems. 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 and the brain vasculature as well as reduced accumulation of amyloid and hyperphosphorylated tau in respective amyloid and tauopathy mouse models. However, the impact of GENUS on the glymphatic/lymphatic systems in the clearance of amyloid and tau accumulation is not clear. We will use amyloid and tauopathy mouse models to determine whether and identify the mechanisms by which GENUS enhances paravascular fluid movement and thereby promotes meningeal lymphatic drainage and glymphatic clearance of brain toxic metabolites including those associated with amyloid and tau.

阿尔茨海默病(AD)是一种无法治愈的脑部疾病，其特点是有毒物质逐渐积累淀粉样蛋白和tau蛋白聚集体，部分原因是由于淋巴和脑膜淋巴系统。我们最近证明了使用感官的非侵入性伽玛夹带在伽马频率范围(30-90赫兹)内诱发神经振荡的刺激(属)可以改善各种AD小鼠模型的病理学研究。属的小鼠表现出对小胶质细胞的积极影响，星形胶质细胞和脑血管构筑以及减少淀粉样蛋白和过度磷酸化tau的积累在各自的淀粉样蛋白和直肠系膜病小鼠模型中。然而，属对淋巴/淋巴的影响系统在清除淀粉样蛋白和tau堆积方面的作用尚不清楚。我们将使用淀粉样蛋白和直肠结缔组织疗法用小鼠模型来确定是否和识别类药物增强血管旁血管的机制液体运动，从而促进脑膜淋巴引流和淋巴清除脑毒代谢物，包括与淀粉样蛋白和tau有关的代谢物。