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

NIA-AD家庭研究。自2003年以来，NIA晚发性阿尔茨海默病家族研究(NIA- Load FBS)招募、评估和跟踪了1,756个受晚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、非痴呆的患者 老年人。其中7,925人(82%)拥有DNA，其中7,014人(88.5%)拥有全基因组SNP阵列数据。1340 76%的家系进行了全外显子组或全基因组测序。这些家庭是按种族/民族划分的 多样性：181人(10.3%)是非裔美国人，425人(24.2%)是拉丁裔，138人(7.8%)被列为“其他”(主要是 亚裔)，1,012人是非西班牙裔白人。发放了67626份生物样本，全国发放了830份 国际调查人员已经使用了来自NIA-LOAD的122多份出版物的数据或样本 FBS，包括阿尔茨海默病遗传学联合会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人的脑部尸检，其中 398例(61%)的脑组织正在进行背外侧的批量RNA测序和DNA甲基化 前额叶皮质。我们收集了322名个体的外周血单核细胞 家属的后续探访。我们将继续扩大资源，以支持功能基因组学 增加生物标本收集，包括额外的DNA、血浆、PBMC和死后脑组织 存储在国家阿尔茨海默病和相关疾病中央资料库，分发给 AD研究人员，促进分子图谱工具用于识别药物靶点的预测模型。在.期间 在新冠肺炎大流行期间，我们依靠电信方法进行跟进和招募，并将扩大 这一努力在更新中。我们还将增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tau217(P-tau217)，以提高临床诊断的准确性。 本U24-资源相关合作协议的主要调查人员被要求延长 招募到家族性早发性AD(EOAD)及其成年子女。Eoad代表着更年轻的边界 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，已经开始招募Eoad家庭及其家庭成员。 我们对AD的多代研究方法为确定外显性提供了一个理想的机会 以及在这些不同的家族中发现的遗传变异的遗传性。这些数据将为您提供信息和指导 国际遗传学研究。个人基因和生物标记结果在研究研究中的返回是一种 由于伦理和实践的复杂性，这项任务具有挑战性。我们将得到NIA的建议的通知 关于退还研究成果的工作组。此次更新的目标是提供丰富的基因 以及科学界的生物标志物资源。我们已将该项目重命名为NIA-AD FBS，以包括 阿尔茨海默病发病的整个年龄谱。

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.