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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：
10222930
负责人：
Li-Huei Tsai
金额：
$ 63.78万
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/10222930
关键词：
Aging Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease pathology Amyloid Amyloid Proteins Anesthetics Astrocytes Attenuated Automobile Driving Blood Vessels Brain Brain Diseases Caliber Carotid Stenosis Cells Cerebrospinal Fluid Cerebrovascular system Chronic Complementary Health Coupled Dextrans Disease Endothelial Cells Excision Exhibits Fluorescence Microscopy Fluorescence-Activated Cell Sorting Frequencies Gap Junctions Genetic Transcription Healthcare Immune Impaired cognition Impairment Integrative Medicine Intercellular Fluid Laser injury Light Liquid substance Literature Lymphatic Lymphatic Diseases Lymphatic clearance Maps Mediating Meningeal Meningeal lymphatic system Meninges Metabolic Microglia Microscopy Molecular Monitor Morphology Movement Mus Music Neurons Nitric Oxide Optics Pathogenicity Pathology Pathway interactions Pattern Pericytes Pharmacology Physiologic pulse Physiological Play Population Process Proteins Role Sensory Signal Transduction Smooth Muscle System Tauopathies Testing Tracer Vasoactive Intestinal Peptide aquaporin 4 awake brain parenchyma cisterna magna cognitive function dietary fitness glymphatic clearance glymphatic dysfunction glymphatic flow glymphatic system hyperphosphorylated tau improved functioning in vivo insight loss of function lymph flow lymphatic drainage lymphatic vessel mindfulness mouse model neurotoxic neurovascular neurovascular coupling neurovascular unit novel therapeutic intervention protein aggregation recruit relating to nervous system 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，其特点是毒性物质的进行性积累