Michigan Alzheimer’s Disease Research Center-Supplement

摘要-增刊 我们试图确定阿尔茨海默病和阿尔茨海默病白质组织病理学特征的MR相关性。 相关疾病(ADRD)，通过将MADRC神经病理学核心的资源与其知识库相结合 死后冷冻组织与大量伴随的死前磁共振研究，与资源 MADRC神经成像核心及其先进的磁共振设备由磁共振获取领域的专家组成， 后处理和参数化。宰后组织学研究和宰前影像研究 表明多种病理经常共存，单一病理通常是例外，因为 常见的脑部病变可能源于血管，如脑白质 (WM)病变、微出血和微梗塞。这些病变的临床意义和程度 临床下降的原因尚不清楚，部分原因是常规MRI技术，如T1和T2加权 影像缺乏特异性来进一步描述其病理基础，如脱髓鞘， 神经胶质增生症，或轴突缺失。由诊断为血管性痴呆的捐献者的尸前磁共振研究指导 (VD)、阿尔茨海默病(AD)和神经学完好的捐献者(ND)，我们将分析冷冻尸检 脑组织来自LPVO周围的脑区和无T2异常的脑区。我们会 从这些组织获得高级MR参数(MWF、iHMT和多层、多向扩散) 在7T时，像常规的T1加权和T2加权MRI一样。组织固定， 组织学/免疫组织化学技术和光学显微镜将被用来分类和量化 存在各种病理参数，包括髓鞘密度、小胶质细胞增殖、少突胶质细胞 密度、磷酸化tau、组织铁含量、管壁厚度和淀粉样蛋白沉积。我们的目标是 描述与脑白质不同病理特征相关的MR信号模式 异常现象。定义与不祥的组织病理学特征相关的多模式MR特征， 正常脑白质的MR信号与病理诊断的关系 使我们能够将反映导致认知下降的病理变化的MR特征与那些 与衰老等其他因素有关。建立这种组织-放射学联系将使我们更加关注-- 活体磁共振方法，并允许将其纳入未来的研究，以更准确地监测和预测认知 ADRD下降。除了它的非淀粉样蛋白方法外，这项提议还将多种资源结合在一起 MADRC的核心，涉及密歇根州三所主要大学的专业知识，每所大学都有自己的一套 推动项目向前发展的技能组合。此外，这些努力的原始数据将在其他国家之间共享 中心，以便将来在外地开展协作工作。

ABSTRACT – SUPPLEMENT We seek to define the MR correlates of white matter histopathological features in Alzheimer’s disease and related disorders (ADRD) by combining the resources at MADRC Neuropathology core, with its repository of post-mortem frozen tissue with a wealth of accompanying pre-mortem MR studies, with the resources of MADRC Neuroimaging core and its advanced MR facility comprised of experts in the fields of MR acquisition, post-processing, and parameterization. Post-mortem histological studies and pre-mortem imaging studies indicate that multiple pathologies often co-exist and that single pathologies are often the exception, as demonstrated by the frequent presence of brain lesions of presumed vascular origin, such as white matter (WM) lesions, microbleeds, and microinfarcts. The clinical significance and the degree to which such lesions contribute to clinical decline is unclear, partly because routine MRI techniques such as T1 and T2 weighted imaging lack the specificity to further characterize their pathological underpinnings such as demyelination, gliosis, or axonal loss. Guided by pre-mortem MR studies of donors with a diagnosis of vascular dementia (VD), Alzheimer’s disease (AD), and neurologically intact donors (ND), we will analyze frozen post-mortem tissue both from brain regions surrounding LPVO’s and brain regions without any T2 abnormalities. We will obtain advanced MR (MWF, ihMT, and multi-shell, multi-directional diffusion) parameters from these tissue blocks as well as conventional T1-weighted and T2-weighted MRI’s at 7T. Tissue fixation, histological/immunohistochemical techniques, and light-microscopy will be used to classify and quantify the presence of various pathological parameters, including myelin density, microglia proliferation, oligodendrocyte density, phosphorylated tau, tissue iron content, vessel wall thickness, and amyloid deposition. Our goal is to characterize the MR signature patterns that correlated with various pathological features in white matter abnormalities. Defining the multi-modal MR signatures that correlate with ominous histopathological features, and the relationship between pathological diagnosis and MR signal in the normal-appearing white matter will allow us to disentangle MR features that reflect pathological changes driving cognitive decline from those that are related to other factors such as aging. Establishing this histo-radiological link will sharpen the focus of in- vivo MR methods and allow their incorporation in future studies to more precisely monitor and predict cognitive decline in ADRD. In addition to its non-amyloid approach, this proposal brings together resources of multiple cores at MADRC and involves the expertise from three major universities in Michigan, each with its own set of skill sets to drive the project forwards. In addition, the raw data from these efforts will be shared among other centers to allow for future collaborative work in the field.