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Tau-induced connectome imaging markers of Alzheimer's disease

Tau 诱导的阿尔茨海默病连接组成像标志物

基本信息

批准号：
10062748
负责人：
Yonggang Shi
金额：
$ 213.06万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10062748
关键词：
Affect Algorithms Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease patient Amyloid Animals Atrophic Autopsy Axon Biological Brain Brain imaging Clinical Communication Communities Corpus Callosum Data Data Set Deposition Diffusion Magnetic Resonance Imaging Disease Disease model Early Diagnosis Elderly Ensure Event Explosion Fiber Goals Health Human Image Impaired cognition Investigation Knowledge Late Onset Alzheimer Disease Latino Lead Learning Magnetic Resonance Imaging Maps Measures Mexican Americans Modeling Network-based Neurofibrillary Tangles Neurons Pathology Pathway interactions Pattern Phase Play Population Positron-Emission Tomography Protocols documentation Public Health Reporting Research Research Personnel Role Senile Plaques Software Tools Staging Surface Symptoms Techniques Time aging brain base cognitive change comparative computerized tools connectome hyperphosphorylated tau imaging biomarker imaging study improved in vivo in vivo Model interest longitudinal analysis multitask neuroimaging novel predictive modeling prion-like targeted imaging tau Proteins tau aggregation tool tractography white matter

项目摘要

Abstract Hyperphosphorylated tau tangle is a defining hallmark of the Alzheimer’s disease (AD). Neuropathological and recent tau PET imaging studies suggest that tau deposition has a much stronger correlation with clinical symptoms than do amyloid plaques. The Braak staging suggests the neuron-to-neuron propagation of tau pathology through axonal pathways, which has been supported with increasing evidence from animal and post- mortem human studies. Limited research, however, has been conducted for the in vivo examination of connectivity changes of fiber pathways involved in tau pathology propagation. There is thus a clear knowledge gap regarding WHEN (specific tau pathology stage) and WHERE (specific fiber pathways) tau-induced connectivity changes occur during the disease course of AD. Building upon our extensive track record in connectome modeling and brain surface mapping, in this project we will develop novel computational tools for the systematic examination of different types of fiber pathways involved in the propagation of tau pathology: the short association fibers in the superficial white matter (SWM), the long association fibers within each hemisphere, and the commissural fibers connecting the two hemispheres. Our project will leverage existing tau PET and connectome imaging datasets that include: ADNI3 for late onset AD (LOAD) and the Estudio de la Enfermaded de Alzheimer en Jalisciences (EEAJ) study for autosomal dominant AD (ADAD). This provides us the unique opportunity to study ADAD and LOAD as being on an AD continuum and obtain a more complete characterization of the fiber pathways affected by the tau pathology from the early prodromal stage to the ultimate onset of AD. In addition, we will use an independent dataset (n=2000) from the Health & Aging Brain among Latino Elders (HABLE) study to validate the generalizability of our computational tools and connectome imaging makers to the Mexican American population. There are three specific aims in this project: 1. To develop novel computational tools for measuring superficial and deep white matter connectivity associated with tau propagation. 2. To map tau-induced connectivity changes of fiber pathways in AD. 3. To develop connectome-based prediction of tau- related cognitive changes in AD. Our project will for the first time provide the comprehensive and in vivo characterization of the fiber pathways affected by tau pathology in AD. This will help elucidate the role of different fiber pathways in the propagation of tau pathology at different disease stages, in particular the U-fibers in the SWM and the commissural fibers responsible for inter-hemispheric communications. The results from our study will provide more targeted connectome imaging makers for the early prediction of AD, especially in studies without tau PET imaging. All computational tools developed in this project will be freely distributed to the research community to enable other AD imaging researchers for more robust and thorough investigation of tau pathology networks.

抽象的过度磷酸化的 tau 蛋白缠结是阿尔茨海默病 (AD) 的一个明显标志。神经病理学和最近的 tau PET 成像研究表明 tau 沉积与临床有更强的相关性症状比淀粉样斑块更严重。 Braak 分期表明 tau 蛋白在神经元之间传播通过轴突通路进行病理学研究，这得到了越来越多的动物和术后证据的支持人体尸检研究。然而，对体内检查进行的研究有限。参与 tau 病理传播的纤维通路的连接性变化。这样就有了明确的认识关于何时（特定 tau 病理阶段）和何处（特定纤维通路）tau 诱导的差距 AD 病程中会发生连接变化。建立在我们广泛的记录之上连接组建模和大脑表面绘图，在这个项目中，我们将开发新颖的计算工具对参与 tau 病理学传播的不同类型纤维通路进行系统检查：浅层白质（SWM）中的短关联纤维，每个半球内的长关联纤维，以及连接两个半球的连合纤维。我们的项目将利用现有的 tau PET 和连接组成像数据集包括：用于晚发 AD (LOAD) 的 ADNI3 和 Estudio de la Enfermaded de Alzheimer en Jalisciences (EEAJ) 针对常染色体显性 AD (ADAD) 的研究。这为我们提供了独特的有机会研究 ADAD 和 LOAD 作为 AD 连续体并获得更完整的表征从早期前驱阶段到 AD 最终发病期间受 tau 病理学影响的纤维通路。此外，我们将使用来自拉丁裔老年人健康与老龄化大脑的独立数据集（n=2000） (HABLE) 研究验证我们的计算工具和连接组成像制造商对墨西哥裔美国人人口。该项目有三个具体目标： 1. 开发新颖的计算方法用于测量与 tau 传播相关的浅层和深层白质连接性的工具。 2. 地图 AD 中 tau 诱导的纤维通路连接性变化。 3. 开发基于连接组的 tau 预测 AD 相关的认知变化。我们的项目将首次提供全面的体内 AD 中受 tau 病理学影响的纤维通路的特征。这将有助于阐明不同的角色不同疾病阶段 tau 病理学传播中的纤维途径，特别是 U 纤维 SWM 和负责半球间通讯的连合纤维。我们的研究结果将为 AD 的早期预测，特别是在研究中提供更有针对性的连接组成像技术没有 tau PET 成像。该项目开发的所有计算工具将免费分发给研究人员社区使其他 AD 成像研究人员能够对 tau 病理学进行更稳健和彻底的研究网络。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A probabilistic atlas of locus coeruleus pathways to transentorhinal cortex for connectome imaging in Alzheimer's disease.

用于阿尔茨海默病连接组成像的蓝斑通路到内嗅皮层的概率图谱

DOI：
10.1016/j.neuroimage.2020.117301
发表时间：
2020-12
期刊：
NeuroImage
影响因子：
5.7
作者：
Sun W;Tang Y;Qiao Y;Ge X;Mather M;Ringman JM;Shi Y;for Alzheimer's Disease Neuroimaging Initiative
通讯作者：
for Alzheimer's Disease Neuroimaging Initiative

Flow-based Geometric Interpolation of Fiber Orientation Distribution Functions.

纤维取向分布函数的基于流的几何插值。