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CSF Clearance in Sporadic Alzheimer's Disease

散发性阿尔茨海默病的脑脊液清除率

基本信息

批准号：
10606516
负责人：
Yi Li
金额：
$ 75.94万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10606516
关键词：
Abeta clearance Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease model Alzheimer&apos s disease therapeutic Amyloid Amyloid beta-Protein Amyloid deposition Anatomy Area Astrocytes Atrophic Binding Biological Markers Blood Brain Brain Pathology Brain imaging Brain region Cerebrospinal Fluid Characteristics Clinical Clinical Trials Cognition Communication Core-Binding Factor Data Deposition Development Disease Progression Dose Drainage procedure Elderly Enrollment Epidemiology Excision Failure Follow-Up Studies Functional disorder Human Image Impaired cognition Impairment Intercellular Fluid Lesion Longitudinal Studies Magnetic Resonance Imaging Measures Methods Molecular Weight Nerve Degeneration Neurofibrillary Tangles Paper Pathology Positron-Emission Tomography Prevention Publications Publishing Reproducibility Research Research Design Research Personnel Risk Factors Role Senile Plaques Standardization Techniques Testing Thick Tracer Ventricular Work abeta deposition cerebral atrophy cognitive function cognitive performance expectation experience follow-up glymphatic clearance glymphatic function glymphatic system improved invention neuropathology novel radiotracer recruit research clinical testing solute tau Proteins therapeutic target water channel β-amyloid burden

项目摘要

PROJECT SUMMARY / ABSTRACT CSF drainage pathology, a potential new Alzheimer's disease (AD) therapeutic target, has been hypothesized as impaired in AD and demonstrated in AD models. There is no non-invasive technique to measure the brain CSF clearance (BCC) in humans. Low molecular weight PET tracers such as 18F-MK6240, 18F-THK5351 and 11C-PiB, like other ISF solutes, rapidly enter and clear the brain. They can freely pass the BBB, distribute into brain and ISF spaces, and move into the ventricular CSF through the glymphatic system. We have developed a method to use radiotracer clearance from brain as a biomarker for glymphatic clearance. Our recent paper and preliminary dynamic PET studies demonstrate that radiotracer distribution in ventricular CSF from 35 to 60 minutes (vCSF-AUC) is a valuable marker to estimate BCC. Our preliminary data demonstrate that after controlling for blood tracer levels, vCSF-AUC are highly reproducible within subjects across tau and amyloid PET tracers and achieve 90% accuracy for group separation between normal and impaired subjects. BCC correlated inversely with brain amyloid deposition, cognitive performance and cortical thickness even after controlling for confounds. These observations justify our proposed 2-year longitudinal study to evaluate the vCSF-AUC as a global predictor of Aβ deposition. Secondarily, we will examine the clearance deficit in early stages of AD and association with features of neurodegeneration (atrophy and cognitive function). This study is a novel attempt to improve our understanding of a proposed mechanism for AD. We anticipate this project will facilitate research into the development of risk factors, epidemiology, prevention and treatment of AD.

项目摘要/摘要