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

基本信息

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
项目类别：
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

项目摘要

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）：该 R21 的主要目标是生成新型 PET 扫描（tau-PET）在诊断为原发性进行性失语症 (PPA) 和三种公认的 PPA 变体的受试者中的行为数据：语法、语义和语言减少的 PPA。病理学研究发现，tau 蛋白是神经退行性疾病的主要原因之一。然而，直到最近，我们还无法确定生命期间大脑中是否存在 tau 蛋白沉积，最近开发出了一种成像配体 AV-1451（以前称为 18F-T807），它与人脑中的 tau 蛋白特异性结合。尚无研究使用神经影像学研究 PPA 中的 tau 结合在 R21 的 2 年里，我们将招募具有所有三种 PPA 变体的受试者并比较 AV-1451 的结合。 PPA 和 PPA 变体与正常对照受试者中的 AV-1451 结合，以估计有多少比例的 PPA 受试者和 PPA 变体对 AV-1451 的 tau 检测呈阳性。我们还将评估是否有任何证据表明 AV-1451 的结合模式。 tau 在这三种 PPA 变体中存在差异。在我们的最终目标中，我们将使用无偏见的聚类分析技术来确定基于 tau 结合模式的临床解剖学定义的 PPA 变体是否有任何支持。与 AV-1451 无关，独立于临床定义的 PPA 变体，鉴于 tau-PET 是一项新技术，可用于假设检验的现有数据很少，因此这些是推动该领域发展所必需的重要步骤。 b 对于为未来的 R01 生成假设非常重要。为了实现我们的目标，我们将进行详细的神经学、言语和语言以及神经心理学测试，以及新的 AV-1451 PET 扫描和测试。此项资助的首席研究员 Keith Josephs 博士是一位世界著名的神经退行性疾病专家，他组建了一支由世界知名的言语和语言专家（Joseph Duffy 博士）、神经影像学（Clifford Jack、Val 博士）组成的团队。 Lowe、Jennifer Whitwell）和神经心理学（Mary Machulda 博士）共同致力于实现这一目标，该团队将拥有最先进的设施和设备来实现这一目标。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Volumetric analysis of hippocampal subregions and subfields in left and right semantic dementia.

左右语义痴呆海马亚区和亚域的体积分析。

DOI：
发表时间：
2024
期刊：
影响因子：
4.8
作者：
Carlos, Arenn F;Weigand, Stephen D;Duffy, Joseph R;Clark, Heather M;Utianski, Rene L;Machulda, Mary M;Botha, Hugo;Thu Pham, Nha Trang;Lowe, Val J;Schwarz, Christopher G;Whitwell, Jennifer L;Josephs, Keith A
通讯作者：
Josephs, Keith A

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：
发表时间：
2018-04
期刊：
影响因子：
0.8
作者：
Utianski, Rene L;Duffy, Joseph R;Savica, Rodolfo;Whitwell, Jennifer L;Machulda, Mary M;Josephs, Keith A
通讯作者：
Josephs, Keith A

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

原发性进行性言语失用症和失语症网络脑电图测量的初步报告。

DOI：
发表时间：
2022-03-12
期刊：
影响因子：
3.3
作者：
Utianski, Rene L;Botha, Hugo;Caviness, John N;Worrell, Gregory A;Duffy, Joseph R;Clark, Heather M;Whitwell, Jennifer L;Josephs, Keith A
通讯作者：
Josephs, Keith A