Imaging and genetic biomarkers for Alzheimer's disease

描述(申请人提供)：阿尔茨海默病(AD)目前影响着500多万美国人，预计到2050年将影响1500万人。目前，生物标志物是诊断和量化潜在AD阶段疾病相关变化的唯一可行方法，在此期间，成功的疾病修正治疗干预将实现最大的影响。高通量神经成像和遗传学在关键地促进我们对疾病机制的理解和促进治疗开发方面有着被证明的记录。我们的目标是开发一个多模式生物标记物AD风险评估工具，使用预期收集的成像、遗传和基因表达ImaGene数据集。我们建议应用先进的成像遗传学统计方法来实现以下三个目标：1)识别与AD相关的候选成像和遗传生物标记物的发现集；2)选择与AD具有强烈生物学相关性的基因表达变量；以及3)开发和验证能够准确评估一个人未来转化为AD的风险的多模式分类器。关键疾病相关途径的发现将从根本上促进我们对AD的分子和遗传触发因素的理解，并使我们更接近基于基因组的干预和个性化的风险评估。

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) presently affects over 5 million Americans and is projected to affect 15 million by 2050. Biomarkers are presently the only feasible approach for diagnosing and quantifying disease-associated changes in the latent AD stage during which a successful disease-modifying therapeutic intervention would realize the greatest impact. High-throughput neuroimaging and genetics have a proven track record for critically advancing our understanding of disease mechanisms and promoting therapeutic development. Our goals are to develop a multimodal biomarker AD risk assessment tool using the prospectively collected imaging, genetic and gene expression ImaGene data set. We propose to apply advanced imaging genetics statistical approaches to achieve the following three aims: 1) identify a discovery set of AD-relevant candidate imaging and genetic biomarkers; 2) select gene expression variables with strong evidence for biological relevance to AD; and 3) develop and validate a multimodal classifier capable of accurately assessing one's risk for future conversion to AD. The discovery of critical disease-related pathways will fundamentally advance our understanding of the molecular and genetic triggers of AD and bring us closer to genomic-based interventions and personalized risk assessment.