Wisconsin Registry for Alzheimer's Prevention: Sex Differences in DNA Methylation

描述（由申请人提供）：目前估计有530万美国人患有阿尔茨海默病（AD），随着婴儿潮一代的老龄化，这一数字预计将迅速增加。越来越多的人认为，AD代表了一种脑衰竭的晚期状态，在此之前有多年的病理变化。目前的治疗方法的有效性有限，最近的临床试验未能确定有效的治疗方法，表明目前的治疗方法是在疾病的晚期阶段进行干预，此时显着改善的可能性较小。早期干预的一个主要障碍是我们缺乏关于哪些生物或环境因素与认知下降相关并最终导致轻度认知障碍（MCI）或AD临床综合征的知识。威斯康星州阿尔茨海默病预防登记处（WRAP）是一项纵向队列研究，包括1，527名有和没有AD家族史的中年人，旨在确定与AD最早体征相关的遗传和环境因素。这项研究的目的是以2年为间隔进行认知、实验室和神经影像学评估，以确定影响目前无症状但患病风险增加的人中A生物标志物表达的健康、生活方式和遗传风险因素。本研究将联合收割机结合过去10年收集的生物标志物测量值和本次更新收集的生物标志物、遗传和环境数据，以描述临床前AD的神经生物学。目前，临床前AD中生物标志物变化的时间进程以及在临床症状发展之前的十年期间影响变化的因素尚不清楚。这些信息对于开发临床试验评估旨在延迟AD发作或减缓AD进展的疾病修饰疗法至关重要。

DESCRIPTION (provided by applicant): An estimated 5.3 million Americans currently have Alzheimer's disease (AD), and the number is expected to increase rapidly with the aging of the baby boom generation. There is a growing consensus that AD represents an advanced state of brain failure that is preceded by many years of pathological changes. The limited effectiveness of current therapies and the failure of recent clinical trials to identify effective therapies for D suggest that current treatments are intervening at a late stage of the disease when significant improvement is less likely. A major barrier to early intervention is our lack of knowledge about which biologic or environmental factors are associated with cognitive decline and eventually result in the clinical syndromes of mild cognitive impairment (MCI) or AD. The Wisconsin Registry for Alzheimer's Prevention (WRAP) is a longitudinal cohort study of 1,527 middle-aged persons with and without a family history of AD that is designed to identify genetic and environmental factors that are associated with the earliest signs of AD. The purpose of this research is to conduct cognitive, laboratory and neuroimaging assessments at 2-year intervals to identify the health, lifestyle and genetic risk factors that influence biomarker expression of A in persons who are currently asymptomatic, but are at an increased risk of developing the disease. This study will combine biomarker measurements collected over the past 10 years with biomarker, genetic and environmental data collected with this renewal to describe the neurobiology of preclinical AD. At the present time, the temporal course of biomarker changes in preclinical AD, and the factors that influence change during the decade before the development of clinical symptoms are unknown. This information is essential for the development of clinical trials evaluating disease-modifying therapies designed to delay the onset or slow the progression of AD.