Functional characterization of Alzheimer's disease associated genetic variants

项目概要/摘要 阿尔茨海默病（AD）是一种破坏性的复杂神经退行性疾病，影响10%的人 超过65岁，无法治愈。拟议研究的总体目标是确定和功能特性 利用新型功能基因组方法和iPSC衍生的细胞模型的AD相关SNP。我们 计划包括：（1）确定候选SNP在三个iPSC驱动的2D AD相关基因中的功能意义。 细胞类型。(2)在三种iPSC驱动的2D AD相关细胞中鉴定由远端非编码SNP调控的基因 类型(3)测试来自（1）和（2）的高置信度AD rSNP在同基因iPSC中的生物学后果。 衍生的2D细胞培养物和3D迷你脑类器官。设计的研究将是非常全面的第一次 AD相关SNP的研究，因此将阐明非编码遗传变异如何有助于 AD.获得AD基本遗传机制的知识将扩大我们的视野， 改进的预防和诊断方法，并产生新的治疗干预的目标， 最终治愈AD

Project Summary/Abstract Alzheimer's disease (AD) is a devastating complex neurological degenerative disorder affecting 10% of people over 65 with no cure. The overarching goal of the proposed study is to identify and functionally characterize AD-associated SNPs utilizing novel functional genomic approaches and iPSC-derived cellular models. Our plans include: (1) Determine the functional significance of candidate SNPs in three iPSC-drived 2D AD relevant cell types. (2) Identify genes regulated by distal non-coding SNPs in three iPSC-drived 2D AD relevant cell types. (3) Test the biological consequences of high confidence AD rSNPs from (1) and (2) in isogenic iPSC- derived 2D cell cultures and 3D minibrain organoids. The designed study will be very first comprehensive investigation of AD associated SNPs, thus will shed light on how non-coding genetic variations contribute to AD. Obtaining knowledge for the fundamental genetic mechanisms of AD will expand our horizons to develop improved preventative and diagnostic methods, and also yield targets for novel therapeutic interventions, ultimately leading to a cure for AD.