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.

阿尔茨海默氏病（AD）是一种无法治愈的脑疾病，以有毒的逐渐积累为特色淀粉样蛋白和tau蛋白聚集体部分是由于散晶和糖的清除受损而引起的脑膜淋巴系统。我们最近表明，使用感觉的无创伽马夹带刺激（属）诱导伽马频率范围内的神经振荡（30-90 Hz）可以改善各种AD鼠标模型中的病理。受到属状态的小鼠对小胶质细胞表现出积极影响，星形胶质细胞和脑脉管系统以及淀粉样蛋白和高磷酸化TAU的积累降低在各自的淀粉样蛋白小鼠模型中。但是，属对淋巴/淋巴的影响清除淀粉样蛋白和TAU积累的系统尚不清楚。我们将使用淀粉样蛋白和tauopathy 小鼠模型以确定并确定属增强链血管的机制液体运动，从而促进脑膜淋巴引流和脑部有毒的胶囊清除率代谢物，包括与淀粉样蛋白和Tau相关的代谢物。