Association of Tau and Neuronal Hypometabolism with Positron Emission Tomography in Alzheimer's Disease

阿尔茨海默病中 Tau 蛋白和神经元代谢减退与正电子发射断层扫描的关联

基本信息

批准号：
10386558
负责人：
Michael Tran Duong
金额：
$ 5.18万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-02-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10386558
关键词：
Age Alzheimer&apos s Disease Alzheimer&apos s disease diagnosis Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Alzheimer&apos s disease therapy Amyloid Area Atrophic Biological Biological Markers Blood Vessels Brain Infarction Cerebrospinal Fluid Cerebrovascular Disorders Cerebrum Classification Clinical Clinical assessments Cognition Cognitive Data Dementia Diagnosis Disease Disease Management Disease Progression Dissociation Educational Background Event Gender Genetic Genotype Goals Growth Human Image Image Analysis Impaired cognition Individual Investigation Ischemia Lead Light Link Machine Learning Magnetic Resonance Imaging Maps Measures Metabolic Metabolism Methods Molecular National Institute on Aging Nature Nerve Degeneration Neurodegenerative Disorders Neurons Participant Pathologic Pathology Patients Pattern Physicians Plasma Positron-Emission Tomography Predisposition Prognosis Publications Pulmonary Embolism Research Risk Signal Transduction Standardization Subgroup Testing Thick Tissues Training Variant White Matter Hyperintensity base burden of illness career deep learning disorder subtype fluorodeoxyglucose fluorodeoxyglucose positron emission tomography follow-up improved in vivo in vivo imaging interest machine learning method mental state molecular imaging neurofilament neuroimaging neuronal metabolism precision medicine preservation protein TDP-43 regional atrophy research study resilience response skills spatiotemporal symposium tau Proteins tau aggregation tool

项目摘要

PROJECT SUMMARY The National Institute on Aging and Alzheimer’s Association recently proposed the ATN framework to systematically classify Alzheimer Disease (AD) in research studies and integrate standardized biomarkers with clinical assessment. The framework is based on binary designations of the presence or absence of amyloid (A), tau (T) and neurodegenerative (N) pathology, wherein AD is defined as A+/T+/N±. This biomarker discretization may simplify AD diagnosis and management but does not enable a more quantitative dissociation of T and N beyond the statement of T+/N±. We are interested in studying neuronal responses to T pathology, including susceptibility (T<N) and resilience (T>N). N has been defined to include structural volume loss (NS) on magnetic resonance imaging (MRI) and lower neuronal metabolism (NM) on positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG). There has not been substantial investigation comparing T with NM, which may necessitate a more nuanced, comparison beyond the binary descriptions. Here, we will utilize the AD Neuroimaging Initiative (ADNI) to investigate the match and mismatch of concomitant T and NM with 18F-flortaucipir and FDG PET. We aim to (1) define “T/NM mismatch” measures derived from several methods including region-of-interest clustering, voxelwise thresholding and deep learning, (2) evaluate the relationships between T/NM mismatch with clinical factors (including cross-sectional and longitudinal cognition, prognosis and progression of T pathology) and (3) assess relationships between T/NM mismatch additional measures of N (including structural NS). Whether in the presence or absence of disease-modifying AD therapy, our in vivo molecular neuroimaging strategy may empower a more comprehensive understanding of the localization and sequence of pathological events leading to AD and unique biological responses to T, including functional resilience.

项目概要美国国家老龄化和阿尔茨海默病协会最近提出了 ATN 框架在研究中系统地对阿尔茨海默病 (AD) 进行分类，并将标准化生物标志物与该框架基于淀粉样蛋白存在或不存在的二元名称（A）， tau (T) 和神经退行性 (N) 病理学，但 AD 被定义为 A+/T+/N± 该生物标志物离散化。可以简化 AD 诊断和管理，但无法更定量地分离 T 和 N 超出T+/N±的表述。我们有兴趣研究对 T 病理学的神经反应，包括敏感性 (T<N) 和恢复力 (T>N) N 被定义为包括磁共振成像 (MRI) 上的结构体积损失 (NS) 和 18F-氟脱氧葡萄糖 (FDG) 正电子发射断层扫描 (PET) 降低神经元代谢 (NM)。目前还没有对 T 与 NM 进行比较的实质性调查，这可能需要更细致的研究，超越二进制描述的比较。在这里，我们将利用 AD 神经影像计划 (ADNI) 来研究伴随的匹配和不匹配 T 和 NM 与 18F-flortaucipir 和 FDG PET 我们的目标是 (1) 定义源自“T/NM 不匹配”的测量。多种方法，包括感兴趣区域聚类、体素阈值和深度学习，(2) 评估 T/NM 不匹配与临床因素（包括横断面和纵向）之间的关系认知、预后和 T 病理进展）和（3）评估 T/NM 不匹配之间的关系 N 的附加措施（包括结构 NS）。无论是否存在缓解疾病的 AD 疗法，我们的体内分子神经影像学策略可以使人们更全面地了解病理的定位和顺序导致 AD 的事件和对 T 的独特生物反应，包括功能恢复力。