Tau PET/CT for Early Detection of Alzheimer’s Disease Pathology

Tau PET/CT 用于早期检测阿尔茨海默病病理学

• 批准号: 10273696
• 负责人: VAL JOHN LOWE
• 金额: $ 39.65万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10273696
• 关键词: Aging; Algorithms; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease pathology; Amyloid; Autopsy; Autoradiography; Biological; Clinic; Clinical; Cognitive; Cohort Studies; Cost Savings; Data; Data Correlations; Databases; Dementia; Deposition; Early Diagnosis; Goals; Immunohistochemistry; Individual; Knowledge; Magnetic Resonance Imaging; Measurement; Methodology; Methods; Neurodegenerative Disorders; Neurofibrillary Tangles; Participant; Pathologic; Pathology; Patients; Pattern; Pharmaceutical Preparations; Phenotype; Positron-Emission Tomography; Prevention trial; Research; Research Personnel; Sampling; Scanning; Selection for Treatments; Senile Plaques; Severities; Severity of illness; Signal Transduction; Subjects Selections; Symptoms; Testing; Tracer; Validation; Work; abeta accumulation; amyloid pathology; cognitive testing; cohort; detection method; high risk; improved; in vivo; indexing; innovation; insight; interest; novel; radiotracer; tau Proteins; therapeutic biomarker; treatment trial; uptake

PROJECT SUMMARY Alzheimer’s disease (AD) is a heterogeneous neurodegenerative disorder characterized by the abnormal accumulation of amyloid-β plaques and neurofibrillary tangles (NFT) composed of tau. Important preliminary data has shown that tau PET with quantitative analysis can distinguish Braak III vs IV NFT pathology. However, there is a gap in knowledge and only limited numbers of participants have been evaluated with early Braak NFT stages (I-IV). We will leverage our database of 1779 participants who have had tau PET over the past 6 years who provide a well characterized cohort for this study at substantial cost savings. Our hypotheses are that novel methods of assessing tau PET will be associated with early Braak NFT stages (I-IV) and cognitive test abnormalities. We will test our hypotheses in three aims: Aim 1: Characterize tau PET measurements that are associated with early NFT. We will use innovative tau PET analysis methods to predict early Braak NFT stage in a large sample of early Braak NFT stage participants. We will use a novel method of quantitative tau PET assessment to improve on prior methodologies and test tau PET for association with early Braak NFT stages. Aim 2: Characterize tau PET features associated with cognitive test findings. We will use tau PET to predict cognitive test findings in CU participants. Cognitive test findings correlate best with tau PET in this regard vs MRI or amyloid PET and tau PET could be an optimal therapeutic biomarker. We will use innovative tau PET imaging analysis methods to predict early cognitive test findings in a large sample of CU. Aim 3: Identify associations of different tau PET radiotracers with early neuropathologic tau hyperphosphorylation and cognitive testing. Alternative tau PET radiotracers may provide improved sensitivity for early NFT pathology and early cognitive findings in CU participants. We will test the differential ability of an alternative tau PET imaging drug to predict early Braak NFT stages and demonstrate association with cognitive tests. This work will provide a rigorous assessment of the biological meaning of tau PET signal. It will have a dramatic impact on treatment algorithms by identifying a subset with early tau deposition and therefore higher risk for developing AD dementia than those with only suspected amyloid pathology. Here we propose a multipronged approach to define tau PET imaging of early NFT and correlation with cognitive test findings in cognitively unimpaired individuals. This proposal is transformative, considering the novel concept of detecting NFT at early stages with state-of-art in vivo PET with novel methods and pathologic correlation that could provide insight for asymptomatic prevention trials.

项目摘要 阿尔茨海默氏病（AD）是一种异质性神经退行性疾病，其特征是 由tau组成的淀粉样蛋白β斑块和神经纤维缠结（NFT）的异常积累。 重要的初步数据表明，具有定量分析的Tau PET可以区分Braak III vs IV NFT病理学。但是，知识存在差距，只有有限的参与者 已经通过早期的Braak NFT阶段（I-IV）进行了评估。我们将利用1779年的数据库 在过去6年中曾拥有Tau Pet的参与者，他们提供了一个具有良好特征的队列的参与者 这项研究以大量的成本节省。我们的假设是评估tau Pet的新方法 将与早期的Braak NFT阶段（I-IV）和认知测试异常有关。我们将测试我们的 三个目标的假设： AIM 1：表征与早期NFT相关的TAU PET测量值。 我们将使用创新的tau宠物分析方法来预测大量样本的早期braak nft阶段 早期的Braak NFT舞台参与者。我们将使用一种新颖的定量tau PET评估方法 改进先前的方法，并测试tau PET与早期Braak NFT阶段相关。 AIM 2：表征与认知测试发现相关的Tau PET特征。 我们将使用Tau PET预测CU参与者的认知测试结果。认知测试结果 在这方面与tau宠物最好的相关 治疗生物标志物。我们将使用创新的Tau PET成像分析方法来预测 大量Cu样本中的认知测试结果。 目标3：确定不同tau宠物放射性示例与早期神经病理学的关联 高磷酸化和认知测试。 替代的tau pet radiotracers可能会提高对早期NFT病理和早期的敏感性 CU参与者的认知发现。我们将测试替代tau PET的差异能力 成像药物以预测早期的Braak NFT阶段，并证明与认知测试的关联。 这项工作将对tau宠物信号的生物学意义进行严格的评估。它将有一个 通过识别早期tau沉积的子集，因此对治疗算法产生巨大影响，因此 与仅怀疑淀粉样病理学的痴呆症的风险更高。我们在这里 提议一种多收益的方法来定义早期NFT的Tau PET成像和与认知的相关性 在认知未受损的个体中测试发现。考虑到这一建议是有变革性的 用新方法使用最先进的体内宠物来检测NFT的新颖概念 和病理相关性，可以为不对称预防试验提供见识。