Amyloid PET in AD, FTLD & PPA: Diagnosis, Functional & Structural Correlations

描述(由申请人提供)：这是一份K-23指导职业发展奖的申请书，题为“AD、FTLD和PPA中的淀粉样蛋白PET：诊断、功能和结构相关性。”这项拟议研究的主要目标是将带有淀粉样β蛋白(AP)配体匹兹堡化合物B(PIB)的PET成像应用于痴呆症的鉴别诊断，同时研究淀粉样蛋白沉积、临床表现以及脑结构和功能之间的关系。阿尔茨海默病(AD)和额颞叶变性(FTLD)是痴呆的两个主要原因，具有不同的组织病理学。原发性进行性失语(PPA)是一种临床综合征，可由FTLD或(较少见的)AD病理引起。PIB是一种新型的PET示踪剂，它特异性地结合AP淀粉样蛋白，这是AD的一个病理标志，不属于FTLD频谱的一部分。本研究的具体目的是：(1)探讨PIB-PET在鉴别AD和FTLD中的作用；(2)确定预测PPA和FTLD中AP淀粉样蛋白存在的临床特征，从而完善诊断标准；(3)利用PIB-PET、FDG-PET和MRI皮质厚度测量方法，研究临床表现、局部AP淀粉样蛋白沉积与神经元功能和结构完整性之间的关系。总体而言，该提案旨在将PIB-PET确立为提高痴呆诊断准确性的重要临床工具，以及研究AP淀粉样蛋白在AD发病机制中作用的重要科学工具。申请者的长期目标是成为痴呆症的独立翻译研究员，拥有结构、功能和分子神经成像方面的专业知识。申请人要求接受以下方面的培训：(1)神经成像，(2)神经病理学和神经生物学-疾病，(S)-生物标记物分析，。(4)生物统计学和。数据分析，(5)认知和系统神经科学，(6)临床痴呆症护理，(7)陈述，复述和赠款撰写，以及(8)负责任的研究行为。培训计划包括实施拟议的研究计划、授课课程以及导师和顾问的指导。痴呆症是与年龄相关的发病率和死亡率的主要原因，并且对卫生保健资源造成越来越大的压力。这项拟议的研究旨在研究一种新的脑成像技术的潜力，以提高痴呆症诊断的准确性，并研究阿尔茨海默病的生物学。

DESCRIPTION (provided by applicant): This is an application for a K-23 Mentored Career Development Award entitled "Amyloid PET in AD, FTLD & PPA: Diagnosis, Functional & Structural Correlations." The primary goal of the proposed research is to apply PET imaging with the amyloid-beta (AP) ligand Pittsburgh Compound-B (PIB) towards the differential diagnosis of dementia, while simultaneously studying the relationships between amyloid deposition, clinical presentation, and brain structure and function. Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are two leading causes of dementia with distinct histopathologies. Primary progressive aphasia (PPA) is a clinical syndrome that can be caused by FTLD or (less commonly) AD pathology. PIB is a novel PET tracer that specifically binds Ap amyloid, a pathologic hallmark of AD that is not part of the FTLD spectrum. The specific aims of this study are: (1) To measure the utility of PIB-PET in distinguishing AD and FTLD; (2) To identify clinical features that predict the presence of Ap amyloid in PPA and FTLD, and thereby refine diagnostic criteria; (3) To study the relationships between clinical presentation, regional Ap amyloid deposition and neuronal functional and structural integrity using PIB-PET, FDG-PET, and MRI-based cortical thickness measurements. Overall, the proposal seeks to establish PIB-PET as an important clinical tool for improving diagnostic accuracy in dementia, and an important scientific tool for studying the role of Ap amyloid in the pathogenesis of AD. The applicant's long-term goal is to become an independent translational investigator in dementia with expertise in structural, functional and molecular neuroimaging. The applicant seeks training in: (1) neuroimaging, (2) neuropathology and neurobiology of -disease, (S)-biomarker analysis,. (4.) .biostatistics and. data analysis, (5) cognitive and systems neuroscience, (6) clinical dementia care, (7) presentation, Dublication and grant writing and (8) responsible conduct of research. The training program includes mplementing the proposed research plan, didactic courses and instruction from mentors and consultants. Dementia is a leading cause of age-related morbidity and mortality, and a growing strain on health-care resources. The proposed research studies the potential of a new brain imaging technique to improve diagnostic accuracy in dementia, and to study the biology of Alzheimer's disease.