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

威斯康星州阿尔茨海默病预防登记处：DNA 甲基化的性别差异

• 批准号: 9236948
• 负责人: Sterling C Johnson
• 金额: $ 10万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9236948
• 关键词: Accounting; Adult; Affect; Age; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease risk; American; Area; Atrophic; Baby Booms; Biological; Biological Factors; Biological Markers; Brain; Child; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Collaborations; Consensus; DNA Methylation; Data; Data Collection; Development; Disease; Disease Progression; Disease susceptibility; Early Intervention; Effectiveness; Environmental Risk Factor; Episodic memory; Etiology; Evaluation; F2-Isoprostanes; Failure; Family history of; Generations; Genetic; Genetic Markers; Genetic Predisposition to Disease; Health; Hippocampus (Brain); Impaired cognition; Individual; Insulin; Insulin Resistance; Interleukin-6; Intervention; Knowledge; Laboratories; Late Onset Alzheimer Disease; Life Style; Link; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Metabolic; Nerve Degeneration; Neurobiology; Obesity; Participant; Pathogenesis; Pathway interactions; Persons; Population; Population Attributable Risks; Populations at Risk; Prefrontal Cortex; Process; Public Health; Registries; Research; Research Design; Research Personnel; Resources; Risk; Risk Factors; Sampling; Sex Characteristics; Staging; Structure; Susceptibility Gene; Symptoms; Syndrome; Time; Treatment Failure; Wisconsin; aged; cerebral atrophy; cognitive change; cohort; data sharing; design; effective therapy; genetic risk factor; genome wide association study; gray matter; imaging biomarker; innovation; meetings; middle age; mild cognitive impairment; neuroimaging; neuropsychological; pre-clinical; preclinical study; predict clinical outcome; social; tau Proteins; therapy design

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.

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)，并且随着婴儿潮一代的老龄化，这一数字预计将迅速增加。人们越来越多地一致认为，AD 代表了一种晚期脑衰竭状态，其之前是多年的病理变化。当前治疗的有效性有限，并且最近的临床试验未能确定 D 的有效治疗方法，这表明当前的治疗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能力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，对象为 1,527 名有或没有 AD 家族史的中年人，旨在识别与 AD 最早迹象相关的遗传和环境因素。本研究的目的是每隔 2 年进行一次认知、实验室和神经影像学评估，以确定目前无症状但患病风险增加的人群中影响 A 生物标志物表达的健康、生活方式和遗传风险因素这种疾病。这项研究将把过去 10 年收集的生物标志物测量结果与本次更新收集的生物标志物、遗传和环境数据结合起来，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过程以及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迟 AD 发病或减缓 AD 进展的疾病缓解疗法的临床试验的开展至关重要。