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.

抽象的高磷酸化的Tau Tangle是阿尔茨海默氏病（AD）的定义标志。神经病理学和最近的tau宠物成像研究表明，tau沉积与临床的相关性更强症状比淀粉样蛋白斑块。 Braak登台表明Tau的神经到神经传播通过轴突途径的病理学，该途径得到了越来越多的动物和后证据的支持 Mortem人类研究。但是，进行了有限的研究，以进行体内检查 Tau病理传播中涉及的纤维途径的连通性变化。因此有清晰的知识关于何时（特定tau病理阶段）和（特定的纤维途径）tau诱导的差距疾病过程中发生连通性的变化发生。以我们广泛的记录为基础连接组建模和脑表面映射，在这个项目中，我们将开发新颖的计算工具对tau病理传播的不同类型的纤维途径的系统检查：浅表白质（SWM）中的短缔合纤维，每个半球内的长关联纤维，以及连接两个半球的连接纤维。我们的项目将利用现有的tau宠物和连接组成像数据集包括：adni3用于延迟发作广告（负载）和eStudio de la enfermaded Alzheimer En Jalisciences（EEAJ）用于常染色体显性AD（ADAD）的研究。这为我们提供了独特的在广告上继续研究ADAD和负载的机会，并获得更完整的表征从早期前驱阶段到AD的最终发作的TAU病理影响的纤维途径。此外，我们将使用拉丁裔长者中的健康与衰老大脑的独立数据集（n = 2000）（Hable）研究以验证我们的计算工具和连接成像制造商的普遍性墨西哥裔美国人。该项目有三个特定的目标：1。开发新颖的计算测量与tau繁殖相关的浅白和深白质连接性的工具。 2。映射 Tau诱导的AD中纤维途径的连通性变化。 3。开发基于连接组的tau- AD的相关认知变化。我们的项目将首次提供全面和体内 AD中受TAU病理影响的纤维途径的表征。这将有助于阐明不同的角色在不同疾病阶段的tau病理传播中的纤维途径，尤其是在 SWM和负责半球间通信的连锁纤维。我们研究的结果将为AD的早期预测提供更多针对性的连接成像制造商，尤其是在研究中没有tau宠物成像。该项目中开发的所有计算工具都将自由分配给研究社区使其他广告成像研究人员对TAU病理学进行更强大和彻底的研究网络。

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

Unsupervised Deep Learning for FOD-Based Susceptibility Distortion Correction in Diffusion MRI.