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
• 负责人: Keith A Josephs
• 金额: $ 23.02万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-15 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9269640
• 关键词: Address; Age; American; Anatomy; Autopsy; Behavior; Binding; Biological Markers; Brain; Brain scan; Characteristics; Classification; Clinical; Clinical Trials; Cluster Analysis; Data; Deposition; Development; Diagnosis; Disease; Equipment; Exploratory/Developmental Grant; Foundations; Funding; Future; Glean; Goals; Grant; Head; Human; Image; Impairment; Knowledge; Language; Language Tests; Lead; Life; Ligands; Link; MAPT gene; MRI Scans; Names; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neuropsychological Tests; Neuropsychology; Pathologic; Patients; Pattern; Pharmacotherapy; Positron-Emission Tomography; Primary Progressive Aphasia; Principal Investigator; Process; Proteins; Protocols documentation; Public Health; Recruitment Activity; Reporting; Retrieval; Semantics; Short-Term Memory; Specialist; Speech; Syndrome; Techniques; Testing; Variant; Work; Writing; aphasic; base; hyperphosphorylated tau; neuroimaging; novel; prospective; public health relevance; research clinical testing; tau Proteins; tau mutation; treatment trial; Address; Age; American; Anatomy; Autopsy; Behavior; Binding; Biological Markers; Brain; Brain scan; Characteristics; Classification; Clinical; Clinical Trials; Cluster Analysis; Data; Deposition; Development; Diagnosis; Disease; Equipment; Exploratory/Developmental Grant; Foundations; Funding; Future; Glean; Goals; Grant; Head; Human; Image; Impairment; Knowledge; Language; Language Tests; Lead; Life; Ligands; Link; MAPT gene; MRI Scans; Names; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neuropsychological Tests; Neuropsychology; Pathologic; Patients; Pattern; Pharmacotherapy; Positron-Emission Tomography; Primary Progressive Aphasia; Principal Investigator; Process; Proteins; Protocols documentation; Public Health; Recruitment Activity; Reporting; Retrieval; Semantics; Short-Term Memory; Specialist; Speech; Syndrome; Techniques; Testing; Variant; Work; Writing; aphasic; base; hyperphosphorylated tau; neuroimaging; novel; prospective; public health relevance; research clinical testing; tau Proteins; tau mutation; treatment trial

 DESCRIPTION (provided by applicant): The primary goal of this R21 is to generate data on the behavior of a new type of PET scan, tau-PET, in subjects diagnosed with primary progressive aphasia (PPA) and the three well recognized variants of PPA: agrammatic, semantic and logopenic PPA. Pathological studies have identified an abnormal protein, tau, as being an important player in the neurodegenerative process. Tau is thought to be one of the leading causes of neurodegenerative diseases. It was not possible however, until recently, to determine whether tau deposition was present in the brain during life. An imaging ligand AV-1451 (formerly 18F-T807) was recently developed, which specifically binds to tau in human brains. No studies have investigated tau binding in PPA using neuroimaging. Over the 2 years of the R21 we will recruit subjects with all three PPA variants and compare AV-1451 binding in PPA and PPA variants, to AV-1451 binding in normal control subjects to get an estimate of what proportion of PPA subjects and PPA variants do test positive for tau with AV-1451. We will also assess whether there is any evidence that binding patterns for tau differs across the three PPA variants. In our final aim we will use the unbiased technique of cluster analysis to determine whether there is any support for clinico-anatomically defined PPA variants based on binding patterns of tau with AV-1451, independent of the clinically defined PPA variants. These are important steps that are necessary to move the field forward given that tau-PET is a new technique with little existing data to draw upon for hypothesis testing. Therefore, this R21 will b important to generate hypotheses for a future R01.The proposal is novel and feasible. To accomplish our aims, we will perform detailed neurological, speech and language, and neuropsychological testing, as well as the new AV-1451 PET scan and volumetric head MRI scanning. The Principal Investigator of this grant, Dr. Keith Josephs is a world renowned neurodegenerative specialist who has assembled a team of world renowned experts in speech and language (Dr. Joseph Duffy), neuroimaging (Drs. Clifford Jack, Val Lowe, Jennifer Whitwell) and neuropsychology (Dr. Mary Machulda) to collectively work to address the aims. The team will have state of the art facilities and equipment in order to do so.

 描述（由适用提供）：该R21的主要目标是生成有关被诊断为主要进行性失血性（PPA）的新型PET扫描，TAU-PET的行为的数据，以及PPA的三种良好认识的变体：Agrammatic，语义，语义，语义和logopenic PPA。病理研究已将异常蛋白Tau确定为神经退行性过程中的重要参与者。 Tau被认为是神经退行性疾病的主要原因之一。但是，直到最近才能确定生命中大脑中是否存在Tau沉积。最近开发了一个成像配体AV-1451（以前为18F-T807），该配体在人类大脑中特异性结合。没有研究使用神经影像学研究了PPA中的tau结合。在R21的两年中，我们将招募具有所有三种PPA变体的受试者，并比较PPA和PPA变体中的AV-1451结合，以与正常对照受试者的AV-1451结合，以估计PPA受试者和PPA变体的比例与AV-1451的TAU测试阳性。我们还将评估是否有任何证据表明三种PPA变体中Tau不同的结合模式。在我们的最终目标中，我们将使用群集分析的无偏见技术来确定基于Tau与AV-1451的结合模式，对临床定义的PPA变体是否有任何支持，与临床定义的PPA变体无关。考虑到tau-pet是一种新技术，几乎没有现有数据可用于假设测试，这些是向前迈进的重要步骤。因此，该R21对于生成未来R01的假设将很重要。该建议是新颖且可行的。为了实现我们的目标，我们将执行详细的神经系统，语音和语言，以及神经心理学测试，以及新的AV-1451 PET扫描和体积的头MRI扫描。这笔赠款的主要研究者基思·约瑟夫斯（Keith Josephs）博士是一位世界著名的神经退行性专家，他召集了一个世界知名的言语和语言专家（Joseph Duffy博士），神经影像学（Drs。CliffordJack，Val Lowe，Val Lowe，Jennifer Whitwell），Jennifer Whitwell）和Neuropsychology（Mary Marchulda博士），以解决该宗旨，以解决该宗旨的工作。该团队将拥有最先进的设施和设备。