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

摘要/摘要 对阿尔茨海默病和相关疾病(ADRD)的了解进展即将产生更多 有效的治疗方法，迫切需要疾病预测生物标记物来指导其使用。vbl.使用 脑脊液中β-淀粉样蛋白和Tau的测量以及正电子发射断层扫描示踪剂， 我们可以在认知正常的人中检测到AD的病理。然而，目前的工具不允许我们预测 无症状病理的个体何时或甚至是否会出现症状。为了满足这一需求，我们 建议在埃默里纵向研究≥3000名认知正常的人(注册时年龄为50-75岁) 一项健康的大脑研究，以确定无症状阿尔茨海默病的频率和种族认知减退率 不同的健康个体队列(具体目标1)。目标1的一个重要目标是实现≥33%非洲- 美国参与者提供足够的力量来解决与种族和性别相关的问题 生物标志物的差异和认知能力下降的风险。参与者将每两年接受一次认知能力测试 检查，心血管生理学，脑核磁共振，以及血液和脑脊液采集。横断面(特定目标2) 纵向分析(特定目标3)将检验这样一种假设，即突触、血管、 髓鞘形成、神经胶质免疫和代谢功能将确定哪些亚群有最大的风险 进展为症状性阿尔茨海默病。候选生物标记物将通过最先进的蛋白质组学来确定， 磁共振成像和统计学方法。高度协作的数据和生物群落共享计划将允许其他 调查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.