Core E: Biosample Core

生物样本核心（E）总结 阿尔茨海默病（AD）的遗传风险因素已经取得了重大进展， 淀粉样前体蛋白和早老素的早发性家族性突变的鉴定 晚发性阿尔茨海默病的风险等位基因，如APOE ε4和超过30个基因座， 协会研究。类似地，用于病理学、β-淀粉样蛋白（Ab，A）和 通过正发射断层扫描（PET）和脑脊液检测， （CSF）。神经变性（N）、神经丝轻链（NfL）-星形胶质细胞增生的其他生物标志物 标志物和胶质酸性胶质细胞蛋白（GFAP）的出现提高了早期疾病诊断的准确性 甚至是AD的前驱期。 尽管取得了这些进展，但在理解和诊断AD方面仍然存在重大局限性。一 大型队列研究的主要局限性是少数民族/种族代表性不足，因为大多数 研究评估了欧洲血统的主要同质群体。这并不反映 在美国、加拿大和全球的跨祖先多样性。例如，最强大的后期- 阿尔茨海默病风险变异体APOE ε4在欧洲人中具有更高的疾病风险 与西班牙裔和非洲裔美国人相比，特别是在只有一个APOE ε4的携带者中， 等位基因 通过PET成像或腰椎穿刺获得的CSF识别AD的生物标志物也很有限 这是由于需要昂贵的技术或侵入性手术。血液生物标志物研究进展 提供了一个可访问的诊断工具，以尽早识别AD的承诺。建立队列， 调查其他群体，如本研究中的亚洲人，对于从种族和 像美国和加拿大这样的多种族国家。 为了解决这一知识缺口，亚洲阿尔茨海默病队列（ACAD） 确立了习该核心的目标是建立遗传数据和血液样本的生物储存库， 研究AD的亚洲人群。有超过5000份DNA样本和3000份血浆和血清 从老年参与者的样本，这将是世界上最大的收集致力于亚洲 在北美的团体。DNA将在NCRAD储存和处理，并由应用中心进行分析。 基因组学，可通过NIAGADS获取数据。NCRAD将使用血浆来测量生物标志物， 淀粉样蛋白tau蛋白神经变性遗传数据和血液生物标志物分析将在项目1和2中完成 并与其他数据集进行比较，以确定亚洲特定的遗传和生物标志物谱， 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.