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

项目总结/摘要 越来越多的证据表明，免疫系统介导的作用和神经炎症可能 与β-淀粉样蛋白一样（或更多）对阿尔茨海默病（AD）发病机制的贡献， 神经缠结标记。可靠、安全且易于重复的神经炎症试验 在疾病发展过程中，给机制研究带来了重大挑战， 治疗发展。为了解决这一未满足的需求，我们开发了神经炎症 成像（NII），用于神经炎症测试的定量成像解决方案。基于扩散 磁共振成像（MRI），NII允许我们非侵入性，非放射性 表征神经炎症的空间分布和时间进展。的 该项目的主要目标是经济有效地描述神经炎症在 通过回顾性分析先前收集的来自NII的扩散MRI数据， 独特的常染色体显性阿尔茨海默病（ADAD）队列。虽然相对较小， AD的病例比例，ADAD呈现与散发性AD相似的病理特征， 可预测的发病年龄和低血管风险因素，由于队列的年轻， 使得该队列在确定神经炎症的时间演变方面非常独特， 在AD中达到高潮。在这个项目中，NII神经炎症生物标志物的轨迹， ADAD的自然过程将被表征和确定。整体之间的联系- 脑NII神经炎症生物标志物和CSF炎症测量（sTREM 2和YKL 40） 将被审查。以及NII、淀粉样蛋白、 还将评估通过PET示踪剂测量的tau蛋白沉积和tau蛋白病。成功 回顾性分析先前使用NII收集的ADAD弥散MRI数据， 显著增强了我们对神经炎症在启动和 AD的进展。将NII神经炎症生物标志物整合到DIAN和其他 临床试验研究将提供神经炎症替代生物标志物， 其他病理学指标用于更好的AD诊断、预后和治疗。

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.