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Tau, amyloid, & white matter burden interact to impact brain networks in preclinical Alzheimer’s disease

Tau、淀粉样蛋白、

基本信息

批准号：
9155978
负责人：
Julius C Hedden
金额：
$ 83.57万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2021-03-31
项目状态：
已结题

项目摘要

PROJECT SUMMARY This project investigates the unique and joint impact of tau and amyloid pathology associated with Alzheimer's disease and of white matter hyperintensities of presumed vascular origin on brain network function and cognition, including memory and executive abilities. The overarching hypothesis is that tau, amyloid, and white matter burden interact to specifically disrupt the function of brain networks in which the burden occurs, and will lead to declines in cognitive abilities associated with the disrupted networks. The proposed work builds on recent advances in the connectomics of functional networks within individuals using magnetic resonance imaging and a recently-developed positron emission tomography marker for the visualization of tau burden in humans. The first specific aim tests for differential and interactive influences of tau, amyloid and white matter burden when these pathological markers occur within a brain network. The second specific aim tests for how interactions between tau, amyloid, and white matter burden may lead to declines in cognition over a 3-year period. The proposed work provides novel extensions of recent cross-sectional findings relating network function, pathology, and cognition to critically test whether tau and amyloid burden interact with white matter burden to impact regional network integrity and cognition during the preclinical stage of Alzheimer's disease. If successful, these aims will provide evidence that localized preclinical tau and amyloid pathology and white matter hyperintensities of presumed vascular origin have an interactive impact that contributes to the functional network and cognitive declines commonly observed during aging. This work will help to differentiate processes attributed to typical aging and development from the pathology associated with Alzheimer's disease at its earliest stages. If successful, this work will improve our understanding of how the location of pathology impacts specific brain networks and cognitive abilities, and will provide measures to improve early diagnosis of network or cognitive dysfunction attributable to the location of these pathological markers in individual patients.

项目概要该项目研究了与阿尔茨海默病相关的 tau 蛋白和淀粉样蛋白病理学的独特联合影响疾病和推测血管起源的白质高信号对脑网络功能的影响认知，包括记忆力和执行能力。总体假设是 tau、淀粉样蛋白和白蛋白物质负担相互作用，特别破坏发生负担的大脑网络的功能，并且会导致与网络中断相关的认知能力下降。拟议的工作建立在利用磁共振研究个体功能网络连接组学的最新进展成像和最近开发的正电子发射断层扫描标记，用于可视化 tau 负荷人类。首个针对 tau、淀粉样蛋白和白质差异和相互作用影响的特定目标测试当这些病理标记物出现在大脑网络内时，就会造成负担。第二个具体目标测试如何 tau、淀粉样蛋白和白质负担之间的相互作用可能导致三年内认知能力下降时期。拟议的工作提供了有关网络的最新横截面研究结果的新颖扩展功能、病理学和认知，严格测试 tau 蛋白和淀粉样蛋白负荷是否与白质相互作用在阿尔茨海默病的临床前阶段，影响区域网络完整性和认知的负担。如果如果成功，这些目标将提供证据证明局部临床前 tau 蛋白和淀粉样蛋白病理学以及白蛋白假定的血管起源的物质高信号具有相互作用的影响，有助于功能衰老过程中常见的网络和认知能力下降。这项工作将有助于区分流程归因于与阿尔茨海默病相关的病理学的典型衰老和发育最早的阶段。如果成功，这项工作将提高我们对病理位置如何影响的理解特定的大脑网络和认知能力，并将提供改善网络早期诊断的措施或认知功能障碍归因于这些病理标志物在个体患者中的位置。