Quantification of Neuroinflammation inAlzheimer's Disease Using Diffusion BasisSpectrum Imaging

使用扩散基础光谱成像对阿尔茨海默氏病的神经炎症进行量化

• 批准号: 10192620
• 负责人: Tammie Lee Smith Benzinger
• 金额: $ 68.98万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10192620
• 关键词: Address; Adult Children; Aging; Alzheimer' s Disease; Alzheimer' s disease therapy; Amyloid beta-42; Amyloid beta-Protein; Area; Astrocytes; Autopsy; Autoradiography; Award; Biological Markers; Brain; Brain imaging; Calcium Binding; Calcium ion; Cell Fraction; Cells; Cellularity; Cerebrospinal Fluid; Characteristics; Clinical; Clinical Trials; Cognition; Cognitive; Collection; Data; Dementia; Development; Diagnostic tests; Diffusion; Disease; Disease Progression; Edema; Equilibrium; Formalin; Freezing; Functional disorder; Funding; Glial Fibrillary Acidic Protein; Grant; Histologic; Histopathology; Human; Image; Immune response; Immunohistochemistry; Impaired cognition; Individual; Infiltration; Inflammation; Inflammatory; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Memory; Microglia; Multiple Sclerosis; Mus; Neuraxis; Neurofibrillary Tangles; Outcome; Participant; Pathogenesis; Pathologic; Pathology; Patient Recruitments; Play; Population; Positron-Emission Tomography; Predictive Value; Quantitative Autoradiography; Research; Research Personnel; Role; Sampling; Scanning; Senile Plaques; Senile dementia; Signal Transduction; Specimen; Spinal Puncture; Staging; Stains; Standardization; Testing; Thinking; Tissues; Tracer; United States Food and Drug Administration; United States National Institutes of Health; Universities; Validation; Washington; astrogliosis; axon injury; clinical biomarkers; cognitive testing; cohort; effective therapy; gray matter; healthy aging; imaging biomarker; imaging modality; improved; in vivo; indexing; interest; member; neuroimaging; neuroinflammation; neuropathology; novel; novel marker; novel therapeutic intervention; pre-clinical; pre-clinical assessment; response; spectrograph; targeted treatment; tau Proteins; tau-1; tool; white matter

Project Summary/Abstract The Charles F. and Joanne Knight Alzheimer's Disease Research Center (Knight ADRC) at Washington University was founded as the Memory and Aging Project in 1979. Since that year, it has received continuous funding from the National Institutes of Health (NIH) and now supports an active cohort of nearly 800 participants who undergo longitudinal clinical and biomarker assessments for preclinical and symptomatic Alzheimer's disease (AD). The Knight ADRC is supported by three major NIH awards, the ADRC center grant (P50AG05681, JC Morris PI), the Healthy Aging and Senile Dementia (HASD; AG03991, JC Morris PI, Imaging Core Leader T Benzinger), and the Adult Children Study (ACS, P01 AG026276, JC Morris PI, Project 4 Leader T Benzinger). With this R01, we request funding for a new initiative which will add a novel biomarker of neuroinflammation in AD, diffusion basis spectrum imaging (DBSI) magnetic resonance imaging (MRI). Members of our research team have previously established the validity of DBSI MRI for neuroinflammation in multiple sclerosis, including both in vivo and ex vivo mouse and human studies. We now extend this research to AD, and will perform in vivo validation using positron emission tomography (PET) and ex vivo validation in human post mortem samples, including immunohistochemistry and autoradiography. Our preliminary data supports the predictive value of neuroinflammation markers in the progress from normal cognition to dementia, and in particularly, the promise of DBSI MRI for this, findings which we will validate in this larger study. We hypothesize that DBSI MRI will correspond to regional neuroinflammation in PET scans and that will correspond to areas of microglial infiltration in the autopsy specimens. We hypothesize that this relationship will be present in the earliest preclinical stages of AD, when cerebrospinal fluid (CSF) has abnormally low levels of Aβ but does not yet demonstrate abnormal levels of tau. Because DBSI MRI requires only Food and Drug Administration (FDA) approved MRI sequences, it could be rapidly extended to clinical trials or clinical populations.

项目摘要/摘要 华盛顿查尔斯·F·奈特和乔安妮·奈特阿尔茨海默病研究中心(奈特ADRC) 大学成立于1979年，名为记忆和老龄化项目。自那一年以来，它已经收到了 来自美国国立卫生研究院(NIH)的持续资助，现在支持一批活跃的 近800名参与者接受了临床前和生物标志物的纵向临床和生物标志物评估 症状性阿尔茨海默病(AD)。骑士ADRC得到了美国国立卫生研究院三大奖项的支持 ADRC中心赠款(P50AG05681，JC Morris Pi)，健康老龄化和老年痴呆症(HASD； AG03991，JC Morris Pi，成像核心领导者T Benzinger)和成人儿童研究(ACS，P01 AG026276，JC Morris Pi，Project 4 Leader T Benzinger)。有了这款R01，我们请求为新的 将在AD中增加一种新的神经炎症生物标志物--扩散基谱成像 (DBSI)磁共振成像(MRI)。我们研究团队的成员之前已经建立了 DBSI MRI对多发性硬化症神经炎的有效性，包括体内和体外 老鼠和人类的研究。我们现在将这项研究扩展到AD，并将使用以下方法进行体内验证 正电子发射断层扫描(PET)和人体死后样本的体外验证，包括 免疫组织化学和放射自显影。我们的初步数据支持以下预测价值 神经炎症标记物在从正常认知到痴呆的过程中，尤其是在 我们将在这项更大的研究中验证这一发现。我们假设 DBSI MRI将与PET扫描中的局部神经炎症相对应，并将与 尸检标本中有小胶质细胞浸润。我们假设这种关系将出现在 阿尔茨海默病最早的临床前阶段，脑脊液中Aβ水平异常低，但 还没有显示出tau的异常水平。因为DBSI MRI只需要食品和药物 美国食品和药物管理局(FDA)批准的MRI序列，可以迅速扩展到临床试验或临床 人口。