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

NIA-AD基于家庭的研究自2003年以来，NIA晚发性阿尔茨海默病家庭为基础的研究（NIA- LOAD FBS）招募、评估并跟踪了1,756个受迟发性阿尔茨海默氏症多重影响的家庭 AD患者，9，682名家庭成员，我们评估并随访了1，096名无关的非痴呆患者， 老人其中7，925（82%）具有DNA，其中7，014（88.5%）具有全基因组SNP阵列数据。1,340 (76%）的家族具有全外显子组或全基因组测序。这些家庭在种族/民族上 多样化：181人（10.3%）是非洲裔美国人，425人（24.2%）是拉丁裔，138人（7.8%）被列为“其他”（主要是 亚裔）和1,012名白色非西班牙裔。已分发67 626份生物样本， 国际研究人员已经使用了来自NIA-LOAD的122多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。 有181人的详细尸检报告，但我们已经完成了655人的大脑尸检， 398例（61%）的脑组织正在进行批量RNA测序和DNA甲基化， 前额皮质我们收集了322个人的外周血单核细胞（PBMC）， 家庭成员的后续访问。我们将继续扩大支持功能基因组学的资源， 增加生物标本采集，包括额外的DNA、血浆、PBMC和死后脑组织 储存在阿尔茨海默病和相关疾病的国家集中储存库， AD研究人员，促进分子分析有助于预测模型，确定药物靶点。期间 在2019冠状病毒病疫情期间，我们依靠电信手段进行跟进和招聘，并将扩大 这一努力在复兴。我们还将添加基于血液的生物标志物Ab 42、Ab 40、总tau（T-tau）、神经丝蛋白（neurofilament 轻链和磷酸化tau 217（P-tau 217）以提高临床诊断的精确度。 本U24-资源相关合作协议的主要研究者被要求延长 招募到家族性早发性AD（EOAD）及其成年子女。EOAD代表较年轻的边界 在AD的整个年龄谱中，APP、PSEN 1和PSEN 2的突变仅部分解释了这一点。 我们已经增加了一个调查小组，已经开始招募EOAD家庭及其家庭成员。 我们对AD的多代研究方法提供了一个理想的机会， 和遗传性的遗传变异在这些不同的家庭。这些数据将提供信息和指导 国际遗传学研究。在一项研究中，个体遗传和生物标志物结果的返回是一种 由于道德和实践的复杂性，这是一项具有挑战性的任务。我们将根据NIA的建议 关于归还研究成果的工作组。这种更新的目标是提供一个丰富的基因， 和生物标志物资源。我们已将该项目重命名为NIA-AD FBS， AD发病的整个年龄范围。

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.