National Institute on Aging Alzheimer's Disease Family-Based Study (NIA-AD FBS)

国家老年阿尔茨海默病家庭研究研究所 (NIA-AD FBS)

• 批准号: 10355812
• 负责人: Gary Wayne Beecham
• 金额: $ 471.4万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10355812
• 关键词: 3-Dimensional; Adult Children; Affect; African American; African American population; Age; Aliquot; Alzheimer' s Disease; Alzheimer’s disease biomarker; Asian; Asian Americans; Autopsy; Biological; Biological Assay; Blood; Brain; C9ORF72; COVID-19 pandemic; Car Phone; Caribbean Hispanic; Cells; Central America; Cerebrovascular Disorders; Clinical Data; Collection; Communities; Consent; DNA; DNA Methylation; Data; Diagnosis; Disease; Drug Targeting; Early Onset Alzheimer Disease; Early Onset Familial Alzheimer' s Disease; Elderly; Ethics; Ethnic group; Family; Family Study; Family member; Freezing; Future; Genetic; Genetic Counseling; Genetic Diseases; Genetic Markers; Genetic study; Genotype; Geography; Goals; Grant; Heritability; Indiana; Individual; International; Late Onset Alzheimer Disease; Latinx; Light; Medical; Methods; Mexican Americans; Molecular Profiling; Mutation; National Institute on Aging; Not Hispanic or Latino; Online Systems; Onset of illness; Participant; Penetrance; Peripheral Blood Mononuclear Cell; Persons; Plasma; Prefrontal Cortex; Principal Investigator; Protocols documentation; Publications; Race; Recommendation; Reporting; Research; Research Personnel; Research Support; Resources; Risk; Risk Factors; SNP array; Sampling; Services; Site; South America; Technology; Telecommunications; Tissues; Travel; U-Series Cooperative Agreements; Universities; Variant; Venous blood sampling; Visit; Work; base; blood-based biomarker; brain tissue; clinical biomarkers; clinical diagnosis; clinical research site; cohort; data sharing; data sharing networks; ethnic diversity; exome; follow up assessment; follow-up; functional genomics; genetic information; genetic variant; genome sequencing; genome wide association study; genome-wide; improved; multi-ethnic; multiple omics; neurofilament; neuropathology; non-demented; novel strategies; offspring; outreach; phenotypic data; predictive modeling; presenilin-1; presenilin-2; racial and ethnic; recruit; repository; research clinical testing; research study; screening; social media; tau Proteins; tau-1; transcriptome sequencing; virtual visit; whole genome; working group

NIA-AD Family-Based Study. Since 2003, the NIA late-onset Alzheimer’s disease Family Based Study (NIA- LOAD FBS) has recruited, assessed and followed 1,756 families multiply affected by late-onset Alzheimer’s Disease (AD), with 9,682 family members, and we have assessed and followed 1,096 unrelated, nondemented elderly. Of these 7,925 (82%) have DNA, and 7,014 (88.5%) of those have genome wide SNP array data. 1,340 (76%) of the families have either whole exome or whole genome sequencing. The families are racially/ethnically diverse: 181 (10.3%) are African American, 425 (24.2%) are Latinx, 138 (7.8%) are listed as “other” (mostly Asian) and 1,012 are white non-Hispanic. 67,626 biological samples have been distributed and 830 national and international investigators have used either data or samples in over 122 publications from the NIA-LOAD FBS, including the Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Sequencing Project. Detailed autopsy reports exist for 181 individuals, but we have completed brain autopsy in 655 from which fresh brain tissue in 398 (61%) are undergoing bulk RNA sequencing and DNA methylation from the dorsolateral prefrontal cortex. We have collected peripheral blood mononuclear cells (PBMCs) from 322 individuals during the follow-up visits of family members. We will continue to expand resources to support functional genomics by increasing biospecimen collections including additional DNA, plasma, PBMCs and postmortem brain tissue stored at the National Centralized Repository for Alzheimer’s Disease and Related Disorders for distribution to AD researchers, facilitating molecular profiling instrumental to prediction models that identify drug targets. During the COVID-19 pandemic, we relied on telecommunication methods for follow-up and recruitment and will expand this effort in the renewal. We will also add blood-based biomarkers Ab42, Ab40, total tau (T-tau), neurofilament light chain and phosphorylated tau 217 (P-tau217) to improve the precision of clinical diagnoses. The principal investigators of this U24-Resource Related Cooperative Agreement were asked to extend recruitment to familial early-onset AD (EOAD) and their adult children. EOAD represents the younger boundary of the entire age spectrum of AD and is only partially explained by mutations in the APP, PSEN1 and PSEN2. We have added an investigative team that has already begun recruiting EOAD families and their family members. Our multigenerational approach to the study of AD offers an ideal opportunity to determine the penetrance and heritability of the genetic variants identified in these diverse families. These data will inform and guide international genetic studies. The return of individual genetic and biomarker results in a research study is a challenging task due to the ethical and practical complexity. We will be informed by the recommendations of NIA working groups regarding the return of research results. The goals of this renewal are to provide a rich genetic and biomarker resource for the scientific community. We have renamed the project as NIA-AD FBS to include the entire age spectrum of AD onset.

NIA-AD基于家庭的研究。自2003年以来，基于NIA晚期的阿尔茨海默氏病家庭研究（NIA- 负载FBS）已招募，评估和遵循1,756个家庭，受到迟到的阿尔茨海默氏症的影响 疾病（AD），有9,682名家庭成员，我们已经评估并遵循了1,096个无关，无关的 老年。在这7,925（82％）中，有DNA，其中7,014（88.5％）具有基因组广泛的SNP阵列数据。 1,340 （76％）家庭具有整个外显子组或整个基因组测序。家庭大致/种族 潜水者：181（10.3％）是非裔美国人，425（24.2％）是拉丁裔，138（7.8％）被列为“其他”（主要是其他”（主要是 亚洲）和1,012是白人非西班牙裔。已分发了67,626个生物样品，830个国家 国际调查人员在NIA负载中使用了122多个出版物中使用了数据或样本 FBS，包括阿尔茨海默氏病遗传学联盟和阿尔茨海默氏病测序项目。 有181个人的详细尸检报告，但我们在655中完成了脑尸检 398（61％）的脑组织正在接受大量的RNA测序和背外侧的DNA甲基化 前额叶皮层。我们已经收集了322名个人的外周血单核细胞（PBMC） 家庭成员的后续访问。我们将继续扩展资源以支持功能基因组学 增加生物循环收集，包括其他DNA，血浆，PBMC和尸体后脑组织 存储在阿尔茨海默氏病和相关疾病的国家集中式存储库中 AD研究人员，支持分子分析，以识别识别药物靶标的预测模型。期间 19009年大流行，我们依靠电信方法进行随访和招聘，并将扩大 这项努力在更新中。我们还将添加基于血液的生物标志物AB42，AB40，Total Tau（T-Tau），神经丝 轻链和磷酸化的TAU 217（P-TAU217）提高了临床诊断的精度。 该U24-Resource相关的合作协议的主要调查员被要求扩展 招募家庭早发广告（EOAD）及其成年子女。 EOAD代表年轻的边界 在AD的整个年龄范围内，仅由应用程序，PSEN1和PSEN2中的突变部分解释。 我们添加了一个调查团队，该团队已经开始招募EOAD家庭及其家人。 我们对AD研究的多代方法为确定渗透率提供了理想的机会 以及这些潜水家庭中确定的遗传变异的遗传力。这些数据将告知和指导 国际遗传研究。单个遗传和生物标志物的回归导致一项研究的研究是 由于道德和实践的复杂性，具有挑战性的任务。 NIA的建议将为我们告知 有关研究结果的返回的工作组。这种续签的目标是提供丰富的遗传 和科学界的生物标志物资源。我们将该项目重命名为NIA-AD FBS AD发作的整个年龄范围。