Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium

摘要 回应PAR-20-099“阿尔茨海默病和相关痴呆的协调” (AD/RD）遗传学、流行病学和临床数据，以增强治疗靶点发现”， 我们组建了一个多学科团队，包括神经成像专家， 神经心理学、液体生物标志物、神经病理学和血管对ADRD的作用 与NIH和阿尔茨海默病测序项目（ADSP）密切合作。我们 ADSP表型协调联盟，或“ADSP-PHC”，寻求协调工作， 与现有的ADSP工作组和倡议，以（1）简化对内表型数据的访问， (2)在多个研究领域提供高质量的内在表型协调， (3)提供关于数据可用性和统一性的全面文件 程序.该项目包括两个协调中心，三个核心，八个领域- 由各自领域世界知名专家领导的具体协调小组。虽然我们的努力将 我们将重点关注数据访问、文档编制和协调，并将与其他ADSP密切合作 工作组和其他大规模协调努力，以最大限度地发挥影响， 国家卫生研究院优先。特别是，我们将重点协调与ADRD相关的内源性表型， 包括从详细的神经心理学评估得出的认知评分， 在离体（尸检时的神经病理学评估）和体内测量神经病理学 （液体生物标志物和正电子发射断层扫描生物标志物）， 损伤（血管危险因素和血管性脑损伤），以及神经退行性变的测量 关注白色（弥散加权MRI）和灰质（T1加权MRI）。的 拟议的协调努力将提供前所未有的机会， ADRD风险和进展的个体生物学贡献者的遗传结构。的 由ADSP-PHC开发的协调数据、协议和教育工具将改变 ADRD格局，加速发现，促进新兴大数据的应用 利用机器学习和人工智能的分析方法。

Abstract In response to PAR-20-099 “Harmonization of Alzheimer’s Disease and Related Dementias (AD/RD) Genetic, Epidemiologic, and Clinical Data to Enhance Therapeutic Target Discovery”, we have assembled a multidisciplinary team that includes experts in neuroimaging, neuropsychology, fluid biomarkers, neuropathology, and vascular contributions to ADRD to work in close partnership with the NIH and the Alzheimer’s Disease Sequencing Project (ADSP). Our ADSP Phenotype Harmonization Consortium, or “ADSP-PHC”, seeks to work in coordination with existing ADSP workgroups and initiatives to (1) streamline access to endophenotype data, (2) provide high quality endophenotype harmonization across multiple research domains, and (3) provide comprehensive documentation of both data availability and harmonization procedures. This project includes two coordinating centers, three cores, and eight domain- specific harmonization teams led by world-renowned experts in their fields. While our efforts will focus on data access, documentation, and harmonization, we will work closely with other ADSP workgroups and other large-scale harmonization efforts to maximize the impact and align with NIH priorities. In particular, we will focus harmonization on ADRD-related endophenotypes, including cognitive scores derived from detailed neuropsychological assessments, measures of neuropathology measured both ex vivo (neuropathological assessment at autopsy) and in vivo (fluid biomarkers and positron emission tomography biomarkers), concomitant pathways of injury (vascular risk factors and vascular brain injury), and measures of neurodegeneration focusing on both white (diffusion-weighted MRI) and grey matter (T1-weighted MRI). The proposed harmonization effort will provide an unprecedented opportunity to disentangle the genetic architecture of individual biological contributors to ADRD risk and progression. The harmonized data, protocols, and educational tools developed by the ADSP-PHC will transform the ADRD landscape, accelerate discovery, and facilitate the application of emerging big data analytic approaches leveraging machine learning and artificial intelligence.