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

 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（由申请人提供）：本R21的主要目标是生成关于新型PET扫描（tau-PET）在诊断为原发性进行性失语症（PPA）和PPA的三种公认变体（语法、语义和逻辑缺失PPA）的受试者中的行为的数据。病理学研究已经确定了一种异常蛋白质tau，它是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。然而，直到最近才能确定tau沉积是否存在于生命过程中的大脑中。最近开发了一种成像配体AV-1451（以前称为18F-T807），其特异性结合人脑中的tau。没有研究使用神经成像研究PPA中的tau结合。在R21的2年中，我们将招募具有所有三种PPA变体的受试者，并将PPA和PPA变体中的AV-1451结合与正常对照受试者中的AV-1451结合进行比较，以估计PPA受试者和PPA变体中AV-1451的tau检测阳性的比例。我们还将评估是否有任何证据表明tau的结合模式在三种PPA变体中存在差异。在我们的最终目标中，我们将使用聚类分析的无偏技术，以确定是否有任何支持临床解剖学定义的PPA变体的基础上结合模式的tau与AV-1451，独立于临床定义的PPA变体。这些都是推动该领域向前发展所必需的重要步骤，因为tau-PET是一种新技术，几乎没有现有数据可用于假设检验。因此，该R21对未来R 01的产生具有重要的B意义。为了实现我们的目标，我们将进行详细的神经学，言语和语言，神经心理学测试，以及新的AV-1451 PET扫描和体积头部MRI扫描。该基金的主要研究者基思约瑟夫博士是一位世界知名的神经退行性疾病专家，他组建了一个由世界知名的语言和语言专家（约瑟夫·达菲博士）、神经影像学专家（克利福德·杰克博士、瓦尔·洛博士、詹妮弗·惠特韦尔博士）和神经心理学专家（玛丽·马彻达博士）组成的团队，共同努力实现目标。该小组将拥有最先进的设施和设备，以便这样做。

项目成果

Molecular neuroimaging in primary progressive aphasia with predominant agraphia.

原发性进行性失语伴显性失写症的分子神经影像学。

• DOI: 10.1080/13554794.2018.1454963
• 发表时间: 2018
• 期刊: Neurocase
• 影响因子: 0.8
• 作者: Utianski,ReneL;Duffy,JosephR;Savica,Rodolfo;Whitwell,JenniferL;Machulda,MaryM;Josephs,KeithA
• 通讯作者: Josephs,KeithA

A Preliminary Report of Network Electroencephalographic Measures in Primary Progressive Apraxia of Speech and Aphasia.

• DOI: 10.3390/brainsci12030378
• 发表时间: 2022-03-12
• 期刊: Brain sciences
• 影响因子: 3.3
• 作者: Utianski RL;Botha H;Caviness JN;Worrell GA;Duffy JR;Clark HM;Whitwell JL;Josephs KA
• 通讯作者: Josephs KA