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

摘要/概要 了解阿尔茨海默病和相关疾病（ADRD）的进展接近产生更多 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 β-淀粉样蛋白和Tau的脑脊液（CSF）测量和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出AD病理。然而，目前的工具不允许我们预测 当或甚至当一个患有无症状病理学的个体将发展出症状时。为了满足这一需求，我们 建议在Emory纵向研究≥3000名认知正常个体（入组时50-75岁） 健康大脑研究，以确定无症状AD的频率和认知能力下降的比率， 健康个体的不同队列（具体目标1）。目标1的一个重要目标是实现非洲人口的 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CSF收集。横截面（具体目标2） 和纵向分析（具体目标3）将检验突触，血管， 髓鞘形成、神经胶质免疫和代谢功能将确定哪些亚组处于最大风险， 进展为症状性AD。将通过最先进的蛋白质组学鉴定候选生物标志物， MR成像和统计方法。一个高度协作的数据和生物标本共享计划将允许其他 研究人员利用这些资源来推进广泛的ADRD研究。

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.