Characterization of the Neuroinflammation in Autosomal Dominant Alzheimer Disease Using Neuro-Inflammation Imaging

项目摘要/摘要 越来越多的证据表明，免疫系统介导的活动和神经炎症可能 对阿尔茨海默病(AD)发病的贡献与β-淀粉样蛋白和 神经原纤维缠结标记。可靠、安全、易重复的神经炎性试验 在疾病发展过程中带来了机械学研究和 治疗的发展。为了解决这一未得到满足的需求，我们开发了神经炎症。 成像(NII)，一种用于神经炎症测试的定量成像溶液。以扩散为基础 磁共振成像(MRI)，NII使我们能够非侵入性、非放射性地 描述神经炎的空间分布和时间进展。这个 该项目的主要目标是以经济高效的方式表征神经炎症在 AD使用NII通过回顾分析先前从 独特的常染色体显性遗传性阿尔茨海默病(ADAD)队列。即使是相对较小的 AD患者中，ADAD呈现出与散发性AD相似的病理特征，具有 由于队列年龄较小，可预测的发病年龄和低血管风险因素， 使该队列在确定神经炎症的时间演变方面非常独特 在公元后达到顶峰。在这个项目中，NII神经炎症生物标记物在 ADAD的自然进程将被描述和确定。整体和整体之间的联系 脑NII神经炎症生物标志物和脑脊液炎症指标(sTREM2和YKL40) 将会被检查。以及神经炎症与NII、淀粉样蛋白之间的关系 还将评估由PET示踪剂测量的沉积和直立不正。成功者 使用NII Will对ADAD患者先前收集的弥散成像数据进行回顾性分析 显著提高我们对神经炎症在启动和恢复过程中的作用的理解 AD的进展。NII神经炎症生物标记物与DIAN等的整合 临床试验研究将提供神经炎替代生物标记物 为更好地诊断、预后和治疗而采取的其他病理措施。

PROJECT SUMMARY/ABSTRACT Mounting evidence shows that immune system-mediated actions and neuroinflammation may contribute as much (or more) to Alzheimer disease (AD) pathogenesis as beta-amyloid and neurofibrillary tangle markers. Reliable, safe, and readily repeatable neuroinflammation tests during disease development have brought significant challenges in mechanistic research and therapy development. To address this unmet need, we developed neuro-inflammation imaging (NII), a quantitative imaging solution for neuroinflammation test. Based on diffusion magnetic resonance imaging (MRI), NII allows us to non-invasively, non-radioactively characterize the spatial distribution and temporal progression of neuroinflammation. The primary goal of this project is to cost-effectively characterize the role of neuroinflammation in AD using NII by retrospectively analyzing previously collected diffusion MRI data from the unique autosomal-dominant Alzheimer's disease (ADAD) cohort. Even though a relatively small proportion of cases of AD, ADAD present the similar pathological features to sporadic AD, has a predictable age at onset and low vascular risk factors due to the young age of the cohort, which makes the cohort very unique to determine the temporal evolution of neuroinflammation that culminates in AD. In this project, the trajectory of NII neuroinflammation biomarkers during the natural course of ADAD will be characterized and determined. The associations between whole- brain NII neuroinflammation biomarkers and CSF inflammation measures (sTREM2 and YKL40) will be examined. And the relationships among neuroinflammation measured by NII, amyloid deposition, and tauopathy measured by PET tracers will also be assessed. The successful retrospective analysis of previously collected diffusion MRI data in ADAD using NII will significantly enhance our understanding of the role of neuroinflammation in the initiation and progression of AD. The integration of NII neuroinflammation biomarkers into the DIAN and other clinical trial studies will provide neuroinflammation surrogate biomarkers complementary to other pathological measures for better AD diagnosis, prognosis, and treatment.