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Locus Coeruleus Biomarker Development for Early Detection of Alzheimers Disease in Humans

用于早期检测人类阿尔茨海默病的蓝斑生物标记物开发

基本信息

批准号：
10194679
负责人：
Anne Shively Berry
金额：
$ 16.25万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10194679
关键词：
Acceleration Address Affect Age Aging Alzheimer disease detection Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease patient Anti-Inflammatory Agents Back Basic Science Blood - brain barrier anatomy Brain Brain region Catecholamines Cell Density Cell Nucleus Chronology Clinical Cognition Cognitive Data Set Detection Development Diagnosis Disease Disease Progression Dopamine Early Diagnosis Early identification Elderly Financial compensation Foundations Health Human Image Individual Individual Differences Infrastructure Injury Magnetic Resonance Magnetic Resonance Imaging Maintenance Measures Medial Mediating Memory Mental disorders Metabolism Methods Midbrain structure Modeling Nerve Degeneration Neuromodulator Norepinephrine Oxidative Stress Parkinson Disease Participant Pathologic Pathology Patients Pattern Performance Play Positron-Emission Tomography Process Property Radioactive Tracers Reporting Research Research Personnel Resolution Role Signal Transduction Sleep Source Stress Structure Substantia nigra structure Symptoms System Temporal Lobe Testing Therapeutic Intervention Tyrosine Validation abnormally phosphorylated tau amyloid pathology biomarker development cognitive neuroscience efficacy testing healthy aging hyperphosphorylated tau imaging approach imaging biomarker imaging modality in vivo interest locus ceruleus structure mild cognitive impairment multimodality neurochemistry neuroimaging neuromelanin neuroregulation norepinephrine system pars compacta predictive marker resilience targeted treatment tau Proteins tau aggregation theories tool young adult

项目摘要

Project Summary The advent of neuroimaging methods for measuring locus coeruleus (LC) structural integrity has generated intense interest from scientific fields focused on Alzheimer’s disease (AD), psychiatric disorders, as well as basic cognitive neuroscience. The LC is the brain’s primary generator of the neuromodulator norepinephrine (NE) and is one of the first brain regions to accumulate hyperphosphorylated tau protein, a hallmark pathological agent in AD. The ability to use magnetic resonance (MR) imaging to assess LC integrity opens up exciting possibilities for earliest detection of disease acceleration, and may also provide an MR measure that captures information about individual differences in neurochemical function. The ability to study neurochemical systems in vivo in humans is limited, with imaging approaches using radioactive tracers being the most established (e.g. positron emission tomography (PET)). However, due to the burden to subjects, as well as the infrastructural challenges, PET imaging is not a tool many researchers use despite the central role neuromodulatory systems like NE play in basic cognition and disease. We will take initial steps towards testing the validity of LC MR measures for predicting NE function by examining the correspondence between a neuromelanin-sensitive MR measure of LC integrity and a PET measure of catecholamine (norepinephrine/dopamine) synthesis capacity ([18F]Fluoro-l-m-tyrosine (FMT)) within subject in healthy young and older adults (Aim 1). Accumulating evidence in healthy aging, AD, and Parkinson’s disease suggests the catecholamine system responds to injury and shows compensatory capacity. Next, we will test the hypothesis that with advancing age, catecholamine synthesis goes up (Aim 2). Finally, to test the utility of LC neuroimaging measures as forecasters of the advancement of tau pathology, we will explore whether neuromelanin-sensitive MR and [18F]FMT predict the accumulation of tau in the medial temporal lobe using tau-sensitive [18F]flortaucipir imaging (Aim 3). Together, this research takes critical steps in establishing MR approaches as sensitive to neurochemical function, examines intriguing mechanisms of neurochemical compensation, and provides empirical testing of models of pathological spread in AD.

项目总结