Imaging tau, amyloid, and neurodegeneration in PPA

PPA 中 tau 蛋白、淀粉样蛋白和神经变性的成像

• 批准号: 9753727
• 负责人: BRADFORD C DICKERSON
• 金额: $ 85.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753727
• 关键词: Address; Affinity; Alzheimer' s Disease; Amyloid; Anatomy; Aphasia; Atrophic; Autopsy; Binding; Biological Markers; Brain; Brain region; Cerebrospinal Fluid; Classification; Clinical; Clinical Research; Clinical Trials; Country; Data; Dementia; Development; Diagnosis; Diagnostic; Diagnostic Specificity; Disease; Enrollment; Face; Frontotemporal Lobar Degenerations; Goals; Image; Individual; International; Kinetics; Language; Language Development; Ligands; Liquid substance; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Methods; Molecular Diagnosis; Monitor; Multimodal Imaging; Nerve Degeneration; Neurodegenerative Disorders; Outcome Measure; Participant; Pathology; Patient Monitoring; Patients; Pattern; Positron-Emission Tomography; Primary Progressive Aphasia; Property; Sampling; Scanning; Signal Transduction; Spatial Distribution; Structure; Suggestion; Symptoms; Syndrome; Technology; Temporal Lobe; Testing; Tracer; Translating; Validity and Reliability; Work; accurate diagnosis; amyloid imaging; amyloid pathology; base; cerebral atrophy; clinical care; clinical phenotype; clinical predictors; cognitive function; design; fluorodeoxyglucose positron emission tomography; frontal lobe; imaging biomarker; imaging modality; improved; in vivo; language impairment; molecular pathology; molecular targeted therapies; next generation; novel imaging technique; prognostic; recruit; tau Proteins; tetrahydrobiopterin; tool

Abstract Primary progressive aphasia (PPA) is a devastating neurodegenerative syndrome that involves relentless development of aphasia with relative sparing of other cognitive functions, at least early in its course. There are multiple subtypes as well as multiple underlying pathologies. PPA and its subtypes can be difficult to differentiate from other neurodegenerative disorders and from each other, particularly early in their course. There are currently few clinical tools to assist in the early specific diagnosis of PPA and its subtypes. We have recently made substantial preliminary progress toward the development of novel imaging techniques that could be extremely valuable in early specific diagnosis of the molecular basis of specific pathologies underlying PPA. We propose to use tau and amyloid imaging tracers to attempt to discriminate these underlying molecular pathologies, and FDG-PET, functional connectivity MRI, and morphometric structural MRI to measure and longitudinally monitor markers of neurodegeneration in the language network(s) and other brain regions. In addition to more accurate diagnosis, these measures will likely be important for prognostication and monitoring of decline and the effects of putative therapies. The overall goal of this proposal is to translate these methods from new scientific technologies into clinically useful tools that can be used by clinicians around the country and internationally to improve the diagnostic specificity and assessment capabilities for PPA and its subtypes.

摘要 原发性进行性失语(PPA)是一种破坏性的神经退行性综合征 这涉及到失语症的持续发展，而其他认知能力相对较差 函数，至少在其过程的早期是这样。有多个子类型，也有多个 潜在的病理。PPA及其子类型可能很难与其他 神经退行性疾病和相互之间，特别是在他们的过程早期。 目前几乎没有临床工具来辅助PPA和PPA的早期特异性诊断 它的子类型。 我们最近在以下方面取得了实质性的初步进展 新的成像技术在早期特异性诊断中可能非常有价值 PPA背后特定病理的分子基础。我们建议使用tau和 淀粉样蛋白成像示踪剂试图区分这些潜在的分子 病理、FDG-PET、功能连接性MRI和形态结构 MRI测量和纵向监测神经退行性变的标志物 语言网络(S)等脑区。除了更准确的诊断外， 这些措施可能对预测和监测下降和 推定疗法的效果。 这项提案的总体目标是将这些方法从新的科学 技术转化为临床有用的工具，可供全国各地的临床医生使用 并在国际上提高诊断特异度和评估能力 PPA及其亚型。