Core E: Biosample Core

生物样本核心(E)摘要 阿尔茨海默病(AD)的遗传风险因素已取得重大进展，从 发现淀粉样前体蛋白和早老素的早发性家族性突变 通过全基因组分析迟发性阿尔茨海默病风险等位基因，如载脂蛋白Eε4和30多个基因座 协会研究。同样，病理学、β-淀粉样蛋白(Ab，A)和 通过正电子发射断层扫描(PET)和脑脊液检测，tau(T)已取得进展 (CSF)。神经退行性变(N)、神经细丝轻链(NFL)--一种星形胶质细胞增生症的其他生物标志物 标志物和胶质酸性纤维蛋白(GFAP)提高了对早期疾病诊断的准确性 分期，甚至先兆到AD。 尽管取得了这些进展，但在理解和诊断AD方面仍然存在重大限制。一个 大型队列研究的主要局限性是多数族裔/少数族裔的代表性不足 研究已经评估了欧洲血统的主要同质性队列。这并不能反映 在美国、加拿大和全球范围内的交叉祖先多样性。例如，最健壮的晚间- 发病阿尔茨海默病风险变异ApoEε4在欧洲人中具有更高的患病风险 与西班牙裔和非裔美国人相比，尤其是在只有一个载脂蛋白Eε4的携带者中 等位基因。 通过PET成像或腰椎穿刺术获得的脑脊液识别AD的生物标记物也有限 由于需要昂贵的技术或侵入性程序。血源性生物标志物的研究进展 提供了一种可访问的诊断工具，以尽早识别AD。建立符合以下条件的队列 调查其他群体，如本研究中的亚洲人，对于从种族和种族角度理解AD至关重要 种族多元化的国家，如美国和加拿大。 为了解决这一知识差距，亚洲阿尔茨海默病队列(ACAD)是 已经成立了。这个核心的目标是建立一个遗传数据和血液样本的生物存储库 亚洲人群用于AD的调查。有超过5000个DNA样本和3000个血浆和血清 来自老年参与者的样本，这将是世界上致力于亚洲人的最大收藏之一 在北美的团体。DNA将在NCRAD存储和处理，由应用研究中心分析 基因组学，通过NIAGADS可以访问数据。NCRAD将使用血浆测量生物标记物 淀粉样蛋白，tau蛋白，神经变性。遗传数据和血液生物标记物的分析将在项目1和2中进行 并与其他数据集进行比较，以识别亚洲特有的遗传和生物标记物图谱， 兴趣和AD诊断检测的阈值。

Biosample Core (E) Summary Significant advances have been made in the genetic risk factors for Alzheimer’s disease (AD), from identification of early onset familial mutations in the amyloid precursor protein and presenilin, to discovery of late onset Alzheimer’s disease risk alleles like APOE ε4 and over 30 loci through genome wide association studies. Similarly, the development of biomarkers for pathology, for beta-amyloid (Ab, A) and Tau (T) have advanced through detection by positive emission tomography (PET) and cerebrospinal fluid (CSF). Additional biomarkers of neurodegeneration (N), neurofilament light chain (NfL)- an astrogliosis marker and glial acidic fibrillary protein (GFAP) have increased the accuracy of diagnosis in early disease stages, or even prodromal to AD. Despite these advances, there still are major limitations to understanding and diagnosing AD. A major limitation of large cohort studies has been the under-representation of ethnic/racial minorities as most studies have evaluated predominantly homogenous cohorts of European ancestry. This does not reflect the cross ancestral diversity in the United States, Canada and globally. For example, the most robust late- onset Alzheimer’s disease risk variant, APOE ε4, confers a higher risk of disease in individuals of European ancestry than it does in Hispanics and African-Americans, particularly in carriers with only one APOE ε4 allele. Biomarkers that identify AD through PET imaging or lumbar puncture-acquired CSF are also limited due to the need for expensive technology or invasive procedures. Advancement of blood-based biomarkers offers promise of an accessible diagnostic tool to identify AD as early as possible. Establishing cohorts that investigate other groups, such as Asians in this study, is critical to understanding AD in ethnically and racially diverse countries like the United States and Canada. To address this gap in knowledge, the Asian Cohort for Alzheimer’s disease (ACAD) was established. The goal of this Core is to establish a biorepository of genetic data and blood samples from Asian populations for the investigation of AD. With over 5000 DNA samples and 3000 plasma and serum samples from elderly participants, it will be one of the largest collections in the world dedicated to Asian groups in North America. DNA will be stored and processed at NCRAD analyzed by the Center for Applied Genomics, with data accessible through NIAGADS. NCRAD will use Plasma to measure biomarkers for amyloid, tau, neurodegeneration. Analysis of genetic data and blood biomarkers will be done in Project 1 and 2 and compared to other datasets to identify Asian-specific genetic and biomarker profiles, genetic variants of interest, and thresholds for diagnostic detection of AD.