Core E: Biosample Core

核心 E：生物样本核心

• 批准号: 10555694
• 负责人: Ho WH Yu
• 金额: $ 83.68万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555694
• 关键词: Address; African American population; Alleles; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Amyloid; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Asian; Asian population; Biological Markers; Blood; Blood specimen; Brain Diseases; Canada; Cerebrospinal Fluid; Clinical; Clinical Research; Cohort Studies; Collection; Communication; Communities; Country; Creatine; DNA; Data; Data Analyses; Data Set; Dedications; Detection; Diagnosis; Diagnostic; Diet; Disease; Disease Progression; Early identification; Elderly; Elements; Ensure; Equipment; Ethnic Origin; Etiology; European; European ancestry; Exercise; Foundations; Gene Mutation; Genetic; Genomics; Glial Fibrillary Acidic Protein; Goals; Heterogeneity; Hispanic Americans; Image; Individual; Investigation; Knowledge; Late Onset Alzheimer Disease; Life Experience; Life Style; Ligands; Light; Magnetic Resonance Imaging; Manuals; Measures; Modality; Mutation; National Institute on Aging; Nerve Degeneration; North America; Participant; Pathologic; Pathology; Pennsylvania; Persons; Plasma; Procedures; Process; Proteins; Race; Research; Research Personnel; Resource Sharing; Resources; Risk; Risk Factors; Sampling; Serum; Site; Socioeconomic Factors; Spinal Puncture; Technology; Therapeutic; Training; United States; Universities; amyloid imaging; astrogliosis; biobank; biomarker development; biomarker performance; blood-based biomarker; clinical investigation; cohort; diagnostic accuracy; diagnostic tool; disorder risk; early onset; ethnic diversity; experience; genetic analysis; genetic risk factor; genetic variant; genome wide association study; global health; high risk; neurofilament; neuroinflammation; polygenic risk score; population stratification; presenilin; quality assurance; racial diversity; racial minority; racial population; recruit; repository; risk prediction; risk variant; sample collection; success; tau Proteins; tau-1; tomography; variant of interest

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.

生物样品核心（E）摘要 阿尔茨海默氏病（AD）的遗传危险因素（AD）已取得了重大进展。 鉴定淀粉样蛋白前体蛋白和presenilin中的早期家族突变，以发现 阿尔茨海默氏病的较晚发病风险等位基因（如apoeε4）和超过30个基因座通过基因组范围 协会研究。同样，用于病理学生物标志物，β-淀粉样蛋白（AB，A）和 tau（t）通过阳性发射断层扫描（PET）和脑脊液进行检测来促进 （CSF）。神经退行性的其他生物标志物（N），神经丝轻链（NFL） - 星形胶质病 标记和神经胶质酸性原纤维蛋白（GFAP）提高了早期疾病诊断的准确性 阶段，甚至是AD前驱。 尽管有这些进步，但仍有主要的理解和诊断广告局限性。 大多数种族/种族少数群体的代表性不足，大多数人的人数不足 研究已经评估了欧洲血统的主要同质同胞。这没有反映 美国，加拿大和全球的跨祖先多样性。例如，最强大的晚期 - 阿尔茨海默氏病风险变体APOEε4赋予欧洲个体疾病风险更高 血统比西班牙裔和非洲裔美国人，特别是在只有一个apoeε4的载体中 等位基因。 通过PET成像或腰穿穿刺获得的CSF识别AD的生物标志物也受到限制 由于需要昂贵的技术或侵入性程序。基于血液的生物标志物的进步 提供可访问的诊断工具的承诺，以尽早识别AD。建立同伙 调查其他群体，例如本研究中的亚洲人，对于在种族中理解广告和 种族多样的国家，例如美国和加拿大。 为了解决这一知识的差距，亚洲阿尔茨海默氏病（ACAD）是 已确立的。该核心的目的是从 亚洲人群进行广告投资。超过5000个DNA样品和3000个血浆和串行 来自最古老的参与者的样本将是世界上最大的收藏品之一 北美的团体。 DNA将在Applied Center分析的NCRAD上存储和处理 基因组学，可以通过Niagads访问数据。 Ncrad将使用等离子体测量生物标志物 淀粉样蛋白，tau，神经变性。遗传数据和血液生物标志物的分析将在项目1和2中进行 并与其他数据集进行了比较以识别亚洲特异性遗传和生物标志物谱， 兴趣和诊断检测的阈值。