Longitudinal multi-modal imaging in progressive supranuclear palsy syndromes

进行性核上性麻痹综合征的纵向多模态成像

基本信息

  • 批准号:
    10468193
  • 负责人:
  • 金额:
    $ 77.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-15 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disorder that is characterized by deposition of the protein 4-repeat (4R) tau in the brain. Patients typically present with postural instability with falls, axial rigidity and vertical supranuclear gaze palsy, although other atypical clinical syndromes occur in which patients present with parkinsonism, freezing of gait, behavioral abnormalities, limb apraxia or speech and language difficulties. In the 1st cycle of the R01 we characterized the cross-sectional and longitudinal behavior of the tau-PET ligand [18F]AV-1451 in PSP and showed that it is related to other neuroimaging measures of neurodegeneration. The 1st cycle focused on the typical clinical presentation of PSP. Since the 1st cycle, a panel of leading experts published new criteria with a standard to diagnose the atypical clinical syndromes. We currently lack understanding of the neurobiology of the atypical PSP syndromes. The primary goal of the 2nd cycle is, therefore, to characterize the clinical, neuroimaging and neuropathological features across typical and atypical PSP syndromes. Specifically, we aim to characterize the cross- sectional and longitudinal multi-modal neuroimaging signatures of the PSP syndromes, determine the relationship between neuroimaging and clinical evolution, and evaluate the autopsy characteristics of the PSP syndromes. We will have data from 160 PSP patients to allow us to address our aims (84 recruited into the 1st cycle and 76 which will be recruited in the 2nd cycle). Each newly recruited patient will undergo the identical examinations as the 84 patients from the 1st cycle, including a neurological and dysphagia evaluation, a 3T magnetic resonance imaging (MRI) that includes structural MRI and diffusion tensor imaging (DTI), and tau- PET using the [18F]AV-1451 ligand. All patients will undergo two serial assessments one year apart. We will assess differences and commonalities in all three neuroimaging modalities across PSP syndromes primarily using a focused region-of-interest approach which will target key brainstem, subcortical and cortical regions that are involved in PSP. We will then ascertain whether the PSP syndromes exhibit unique multi-modal signatures using a classification model. Voxel-level analyses will also be performed to assess patterns across the whole brain. The relationship between clinical evolution, including the evolution of dysphagia, and the PSP syndromes and neuroimaging measures will be assessed. Autopsy examinations will be performed on all patients from both cycles that die and 4R tau burden will be compared across PSP syndromes. We will also determine the degree to which neuroimaging differences across syndromes are related to tau burden and investigate how additional pathologies are associated with the different syndromes. The results of this grant will increase our knowledge of the neural underpinnings of the clinical and anatomical heterogeneity in PSP and will also be essential for the development of optimum biomarkers for PSP that will aid diagnosis, track disease progression and allow patients with all PSP syndromes to be included in future treatment trials.
项目摘要 进行性核上性麻痹(PSP)是一种破坏性的神经退行性疾病,其特征在于: 蛋白质4-重复(4 R)tau在脑中的沉积。患者通常表现为姿势不稳, 福尔斯,轴性强直和垂直核上性凝视麻痹,虽然其他非典型临床综合征发生在 患者表现为帕金森综合征、步态僵硬、行为异常、肢体失用或言语障碍 和语言困难。在R 01的第一个周期中,我们表征了横截面和纵向 在PSP中的tau-PET配体[18 F]AV-1451的行为,并显示其与其他神经影像学相关 神经退行性变的指标第1个周期侧重于PSP的典型临床表现。自1日起 一个由顶尖专家组成的小组发表了一项新的标准, 综合征我们目前缺乏了解的神经生物学的非典型PSP综合征。主 因此,第二周期的目标是表征临床、神经影像学和神经病理学 典型和非典型PSP综合征的特征。具体来说,我们的目标是描述十字架- PSP综合征的横断面和纵向多模态神经影像学特征,确定 神经影像学与临床演变的关系,并评估PSP的尸检特征 综合征我们将获得160名PSP患者的数据,以使我们能够实现我们的目标(84名患者被招募到第一批 76人将在第二个周期招募)。每个新招募的患者将接受相同的 第1个周期的84例患者的检查,包括神经系统和吞咽困难评估,3 T 磁共振成像(MRI),包括结构MRI和扩散张量成像(DTI),以及tau- 使用[18F]AV-1451配体的PET。所有患者将接受两次连续评估,间隔一年。我们将 评估PSP综合征所有三种神经影像学方式的差异和共同点, 使用聚焦感兴趣区域的方法,该方法将针对关键的脑干、皮层下和皮层区域 与PSP有关。然后,我们将确定PSP综合征是否表现出独特的多模态 使用分类模型的签名。还将进行体素级分析,以评估 整个大脑。临床演变(包括吞咽困难的演变)与PSP之间的关系 将评估症状和神经影像学测量。将对所有人进行尸检 将在PSP综合征中比较来自两个周期的死亡和4 R tau负荷的患者。我们还将 确定不同综合征的神经影像学差异与tau负荷相关的程度, 研究其他病理如何与不同的综合征相关。这笔赠款的结果将 增加我们对PSP临床和解剖异质性的神经基础的了解, 对于开发PSP的最佳生物标志物也是必不可少的,这些生物标志物将有助于诊断,跟踪疾病, 并允许所有PSP综合征患者纳入未来的治疗试验。

项目成果

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Keith A Josephs其他文献

Keith A Josephs的其他文献

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{{ truncateString('Keith A Josephs', 18)}}的其他基金

Investigating the role of TMEM106b genetics and pathology in Alzheimer’s disease, LATE and FTLD
研究 TMEM106b 遗传学和病理学在阿尔茨海默病、LATE 和 FTLD 中的作用
  • 批准号:
    10806465
  • 财政年份:
    2023
  • 资助金额:
    $ 77.93万
  • 项目类别:
The neurobiology of two distinct types of progressive apraxia of speech
两种不同类型的进行性言语失用的神经生物学
  • 批准号:
    10224718
  • 财政年份:
    2017
  • 资助金额:
    $ 77.93万
  • 项目类别:
The neurobiology of two distinct types of progressive apraxia of speech
两种不同类型的进行性言语失用的神经生物学
  • 批准号:
    9982934
  • 财政年份:
    2017
  • 资助金额:
    $ 77.93万
  • 项目类别:
The neurobiology of two distinct subtypes of neurodegenerative apraxia of speech: phenotypes of Alzheimer disease related 4-repeat tauopathies
神经退行性言语失用症两种不同亚型的神经生物学:阿尔茨海默病相关 4 重复 tau蛋白病的表型
  • 批准号:
    10654129
  • 财政年份:
    2017
  • 资助金额:
    $ 77.93万
  • 项目类别:
Assessment of hyperphosphorylated tau PET binding in primary progressive aphasia
原发性进行性失语症中过度磷酸化 tau PET 结合的评估
  • 批准号:
    9269640
  • 财政年份:
    2016
  • 资助金额:
    $ 77.93万
  • 项目类别:
Longitudinal Multi-modal Imaging in Progressive Supranuclear Palsy Syndromes
进行性核上性麻痹综合征的纵向多模态成像
  • 批准号:
    10683769
  • 财政年份:
    2015
  • 资助金额:
    $ 77.93万
  • 项目类别:
Longitudinal multi-modal imaging in progressive supranuclear palsy syndromes
进行性核上性麻痹综合征的纵向多模态成像
  • 批准号:
    9894894
  • 财政年份:
    2015
  • 资助金额:
    $ 77.93万
  • 项目类别:
Longitudinal multi-modal imaging in progressive supranuclear palsy syndromes
进行性核上性麻痹综合征的纵向多模态成像
  • 批准号:
    10266026
  • 财政年份:
    2015
  • 资助金额:
    $ 77.93万
  • 项目类别:
Understanding the role of TDP-43 in Alzheimer's disease and FTLD
了解 TDP-43 在阿尔茨海默病和 FTLD 中的作用
  • 批准号:
    9132162
  • 财政年份:
    2010
  • 资助金额:
    $ 77.93万
  • 项目类别:
Understanding the role of TDP-43 in Alzheimer’s disease and FTLD
了解 TDP-43 在阿尔茨海默病和 FTLD 中的作用
  • 批准号:
    10446997
  • 财政年份:
    2010
  • 资助金额:
    $ 77.93万
  • 项目类别:

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