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

描述(申请人提供)：据估计，目前有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。越来越多的人达成共识，认为阿尔茨海默病代表着一种晚期的脑衰竭状态，在此之前会出现多年的病理变化。目前的治疗方法效果有限，最近的临床试验也未能确定有效的治疗方法，这表明目前的治疗方法是在疾病的晚期进行干预，而此时出现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能力下降相关的知识，并最终导致轻度认知障碍(MCI)或AD的临床症状。威斯康星州阿尔茨海默氏症预防登记处(WRAP)是一项纵向队列研究，对1,527名有和没有AD家族史的中年人进行研究，旨在确定与AD最早迹象相关的遗传和环境因素。这项研究的目的是每两年进行一次认知、实验室和神经成像评估，以确定影响A生物标记物表达的健康、生活方式和遗传风险因素，这些因素目前没有症状，但发展为疾病的风险增加。这项研究将结合过去10年收集的生物标记物测量和这次更新收集的生物标记物、遗传和环境数据来描述临床前AD的神经生物学。目前，临床前阿尔茨海默病患者生物标记物变化的时间进程，以及在临床症状出现前十年内影响变化的因素尚不清楚。这些信息对于评估旨在延缓或减缓AD发病或进展的疾病修饰疗法的临床试验的发展至关重要。

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.