The Emory Healthy Brain Study: Discovering Predictive Biomarkers for Alzheimer's Disease

埃默里健康大脑研究：发现阿尔茨海默病的预测生物标志物

• 批准号: 10348719
• 负责人: JAMES J LAH
• 金额: $ 713.81万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10348719
• 关键词: Address; African American; African American population; Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid beta-42; Amyloid beta-Protein; Area; Biological Markers; Blood; Blood Vessels; Brain; Cardiovascular Diseases; Cardiovascular Physiology; Carotid Atherosclerotic Disease; Caucasians; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Characteristics; Chronic Disease; Clinical; Cognitive; Collection; Data; Detection; Diagnosis; Disease; Enrollment; Etiology; Evolution; Exposure to; Frequencies; Functional disorder; Future; Genotype; Goals; Hormone replacement therapy; Immunity; Impaired cognition; Individual; Inflammation; Intervention; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Myelin; Neuraxis; Neurons; Participant; Pathology; Patients; Phenotype; Positron-Emission Tomography; Prevention trial; Preventive treatment; Proteins; Proteomics; Race; Research; Research Personnel; Resources; Risk; Role; Science; Sex Differences; Statistical Methods; Subgroup; Symptoms; Synapses; Techniques; Testing; Time; Tracer; Work; aged; arterial stiffness; asymptomatic Alzheimer' s disease; biomarker discovery; brain magnetic resonance imaging; candidate marker; cardiovascular disorder risk; cerebrovascular; clinical biomarkers; clinical phenotype; clinical practice; cognitive testing; cohort; data resource; data sharing; effective therapy; follow-up; high risk; imaging modality; immune function; longitudinal analysis; middle age; myelination; neuroinflammation; novel marker; pre-clinical; predictive marker; predictive test; prevent; racial diversity; recruit; sex; spectroscopic imaging; support tools; symptom treatment; tau Proteins; tool

Abstract/Summary Progress in understanding Alzheimer’s disease and related disorders (ADRD) is close to producing more effective treatments, creating an urgent need for disease-predictive biomarkers to guide their use. Using cerebrospinal fluid (CSF) measurements of beta-amyloid and Tau and positron-emission tomography tracers, we can detect AD pathology in cognitively normal individuals. However, current tools do not allow us to predict when or even if an individual with asymptomatic pathology will develop symptoms. To address this need, we propose to longitudinally study ≥3000 cognitively normal individuals (50-75 years at enrollment) in the Emory Healthy Brain Study to define the frequency of asymptomatic AD and rates of cognitive decline in a racially diverse cohort of healthy individuals (Specific Aim 1). An important goal of Aim 1 is to achieve ≥33% African- American participants to provide sufficient power to address questions regarding race- and sex-dependent differences in biomarkers and risk of cognitive decline. Participants will be phenotyped biennially with cognitive testing, cardiovascular physiology, brain MRI, and blood and CSF collection. Cross-sectional (Specific Aim 2) and longitudinal analyses (Specific Aim 3) will test the hypothesis that biomarkers of synaptic, vascular, myelination, glial immunity, and metabolic functions will identify subgroups who are at greatest risk of progressing to symptomatic AD. Candidate biomarkers will be identified through state-of-the-art proteomics, MR imaging, and statistical methods. A highly collaborative data and biospecimen sharing plan will allow other investigators to leverage these resources to advance a broad spectrum of ADRD research.

摘要/总结 对阿尔茨海默病及相关疾病 (ADRD) 的了解即将取得进展 有效的治疗方法，迫切需要疾病预测生物标志物来指导其使用。使用 脑脊液 (CSF) 测量 β-淀粉样蛋白和 Tau 以及正电子发射断层扫描示踪剂， 我们可以在认知正常的个体中检测 AD 病理。然而，当前的工具不允许我们预测 当或即使无症状病理个体会出现症状。为了满足这一需求，我们 提议对埃默里大学 ≥3000 名认知正常的个体（入组时 50-75 岁）进行纵向研究 健康大脑研究旨在确定不同种族中无症状 AD 的发生频率和认知能力下降的比率 不同的健康个体群体（具体目标 1）。目标 1 的一个重要目标是实现 ≥33% 的非洲人 美国参与者提供足够的权力来解决有关种族和性别依赖的问题 生物标志物的差异和认知能力下降的风险。参与者将每两年进行一次认知表型分析 测试、心血管生理学、脑部 MRI 以及血液和脑脊液采集。横截面（特定目标 2） 纵向分析（具体目标 3）将检验以下假设：突触、血管、 髓鞘形成、神经胶质免疫和代谢功能将识别出最有风险的亚组 进展为有症状的 AD。候选生物标志物将通过最先进的蛋白质组学来鉴定， MR 成像和统计方法。高度协作的数据和生物样本共享计划将允许其他 研究人员利用这些资源推进广泛的 ADRD 研究。