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， 鉴定淀粉样前体蛋白和早老素的早发家族突变，以发现 晚发性阿尔茨海默病风险等位基因（如 APOE ε4）和全基因组范围内的 30 多个位点 同样，β-淀粉样蛋白（Ab、A）和病理学生物标志物的开发。 Tau (T) 已通过正发射断层扫描 (PET) 和脑脊液检测取得进展 (CSF) 神经变性 (N)、神经丝轻链 (NfL) 的其他生物标志物 - 星形胶质细胞增生 标记物和胶质酸性纤维蛋白（GFAP）提高了早期疾病诊断的准确性 阶段，甚至是 AD 的前驱期。 尽管取得了这些进展，但理解和诊断 AD 仍然存在重大局限性。 大型队列研究的主要局限性是少数族裔/种族的代表性不足，因为大多数研究 研究主要评估了欧洲血统的同质群体，但这并没有反映出来。 例如，美国、加拿大和全球的跨祖先多样性最为强大。 阿尔茨海默氏病发病风险变异体 APOE ε4 使欧洲个体患阿尔茨海默病的风险更高 血统高于西班牙裔和非裔美国人，特别是只有一个 APOE ε4 的携带者 等位基因。 通过 PET 成像或腰椎穿刺获得的脑脊液来识别 AD 的生物标志物也很有限 由于需要昂贵的技术或侵入性手术。 提供了一种易于使用的诊断工具来尽早识别 AD 的队列。 调查其他群体，例如本研究中的亚洲人，对于了解种族和种族方面的 AD 至关重要 美国和加拿大等种族多元化的国家。 为了解决这一知识差距，亚洲阿尔茨海默病队列（ACAD） 该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。 用于研究亚洲人群的 AD 拥有超过 5000 个 DNA 样本和 3000 份血浆和血清。 来自老年参与者的样本，这将是世界上最大的致力于亚洲人的收藏之一 DNA 将在 NCRAD 进行存储和处理，并由应用中心进行分析。 基因组学，可通过 NIAGADS 获取数据，将使用 Plasma 来测量生物标志物。 淀粉样蛋白、tau蛋白、神经变性将在项目1和2中进行遗传数据和血液生物标志物的分析。 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概况、 AD 诊断检测的兴趣和阈值。