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:
- 金额:$ 75.94万
- 依托单位:
- 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:
- 关键词:Abeta clearanceAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease modelAlzheimer&aposs disease therapeuticAmyloidAmyloid beta-ProteinAmyloid depositionAnatomyAreaAstrocytesAtrophicBindingBiological MarkersBloodBrainBrain PathologyBrain imagingBrain regionCerebrospinal FluidCharacteristicsClinicalClinical TrialsCognitionCommunicationCore-Binding FactorDataDepositionDevelopmentDisease ProgressionDoseDrainage procedureElderlyEnrollmentEpidemiologyExcisionFailureFollow-Up StudiesFunctional disorderHumanImageImpaired cognitionImpairmentIntercellular FluidLesionLongitudinal StudiesMagnetic Resonance ImagingMeasuresMethodsMolecular WeightNerve DegenerationNeurofibrillary TanglesPaperPathologyPositron-Emission TomographyPreventionPublicationsPublishingReproducibilityResearchResearch DesignResearch PersonnelRisk FactorsRoleSenile PlaquesStandardizationTechniquesTestingThickTracerVentricularWorkabeta depositioncerebral atrophycognitive functioncognitive performanceexpectationexperiencefollow-upglymphatic clearanceglymphatic functionglymphatic systemimprovedinventionneuropathologynovelradiotracerrecruitresearch clinical testingsolutetau Proteinstherapeutic targetwater channelβ-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
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Neuromodulation Effect of Very Low Intensity Transcranial Ultrasound Stimulation on Multiple Nuclei in Rat Brain.
极低强度经颅超声刺激对大鼠脑内多核的神经调节作用。
- DOI:10.3389/fnagi.2021.656430
- 发表时间:2021
- 期刊:
- 影响因子:4.8
- 作者:Liu Y;Wang G;Cao C;Zhang G;Tanzi EB;Zhang Y;Zhou W;Li Y
- 通讯作者:Li Y
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{{ truncateString('Yi Li', 18)}}的其他基金
Mutating E-cadherin in rats to model lobular breast cancer
突变大鼠 E-钙粘蛋白以模拟小叶乳腺癌
- 批准号:
10830164 - 财政年份:2022
- 资助金额:
$ 75.94万 - 项目类别:
Next Generation Rat Models of ER+ Breast Cancer
下一代 ER 乳腺癌大鼠模型
- 批准号:
10591512 - 财政年份:2022
- 资助金额:
$ 75.94万 - 项目类别:
Next Generation Rat Models of ER+ Breast Cancer
下一代 ER 乳腺癌大鼠模型
- 批准号:
10464834 - 财政年份:2022
- 资助金额:
$ 75.94万 - 项目类别:
New Statistical Methods for Modelling Cancer Outcomes
癌症结果建模的新统计方法
- 批准号:
10542801 - 财政年份:2021
- 资助金额:
$ 75.94万 - 项目类别:
New Statistical Methods for Modelling Cancer Outcomes
癌症结果建模的新统计方法
- 批准号:
10317123 - 财政年份:2021
- 资助金额:
$ 75.94万 - 项目类别:
CSF Clearance in Sporadic Alzheimer's Disease
散发性阿尔茨海默病的脑脊液清除率
- 批准号:
9981182 - 财政年份:2019
- 资助金额:
$ 75.94万 - 项目类别:
CSF Clearance in Sporadic Alzheimer's Disease
散发性阿尔茨海默病的脑脊液清除率
- 批准号:
9993210 - 财政年份:2019
- 资助金额:
$ 75.94万 - 项目类别:
CSF Clearance in Sporadic Alzheimer's Disease
散发性阿尔茨海默病的脑脊液清除率
- 批准号:
10390277 - 财政年份:2019
- 资助金额:
$ 75.94万 - 项目类别:
The Regulation of Gene Expression via Epigenetic Mechanisms during Onset of Obesity, Type 2 Diabetes
肥胖、2 型糖尿病发病期间通过表观遗传机制调节基因表达
- 批准号:
9270051 - 财政年份:2016
- 资助金额:
$ 75.94万 - 项目类别: