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)

基本信息

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
项目类别：
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&apos 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&apos 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

项目摘要

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 年起，NIA 迟发性阿尔茨海默病基于家庭的研究 (NIA- LOAD FBS）已招募、评估并跟踪了 1,756 个受迟发性阿尔茨海默氏症影响的家庭疾病（AD），有 9,682 名家庭成员，我们评估并跟踪了 1,096 名无关的非痴呆患者其中 7,925 名 (82%) 拥有 DNA，其中 7,014 名 (88.5%) 拥有全基因组 SNP 阵列数据。 (76%) 的家庭进行了全外显子组或全基因组测序。多元化：181 名 (10.3%) 为非裔美国人，425 名 (24.2%) 为拉丁裔，138 名 (7.8%) 被列为“其他”（大部分为已分发了 67,626 份生物样本和 830 份全国样本。国际研究人员已使用 NIA-LOAD 超过 122 篇出版物中的数据或样本 FBS，包括阿尔茨海默病遗传学联盟和阿尔茨海默病测序项目。已有 181 人的详细尸检报告，但我们已完成 655 人的脑部尸检，其中新鲜 398 例 (61%) 的脑组织正在接受来自背外侧的大量 RNA 测序和 DNA 甲基化我们收集了 322 名个体的外周血单核细胞 (PBMC)。我们将继续扩大支持功能基因组学的资源。增加生物样本收集，包括额外的 DNA、血浆、PBMC 和死后脑组织存储在阿尔茨海默氏病和相关疾病国家集中存储库中，以便分发给 AD 研究人员，促进分子分析有助于识别药物靶点的预测模型。 COVID-19大流行期间，我们依靠电信方式进行跟进和招聘，并将扩大我们还将在更新中添加基于血液的生物标志物 Ab42、Ab40、总 tau (T-tau)、神经丝。轻链和磷酸化 tau 217 (P-tau217) 以提高临床诊断的精确度。该 U24 资源相关合作协议的主要研究者被要求延长家族性早发性AD（EOAD）及其成年子女的招募代表了年轻的边界。 APP、PSEN1 和 PSEN2 的突变只能部分解释 AD 的整个年龄谱。我们增加了一个调查小组，该小组已经开始招募 EOAD 家庭及其家人。我们对 AD 研究的多代方法为确定外显率提供了理想的机会这些不同家族中发现的基因变异的遗传性和遗传性将提供信息和指导。国际遗传学研究中个体遗传和生物标志物结果的返回是一项研究。由于道德和实践的复杂性，我们将听取 NIA 的建议，这是一项具有挑战性的任务。有关研究成果归还的工作组的目标是提供丰富的遗传信息。我们已将该项目重命名为 NIA-AD FBS，以纳入其中。 AD 发病的整个年龄范围。