Alzheimer's Disease, Genes, and Pesticide Use in the Agricultural Health Study

农业健康研究中的阿尔茨海默病、基因和农药使用

• 批准号: 8911315
• 负责人: BRENDA L PLASSMAN
• 金额: $ 54.63万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-13 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8911315
• 关键词: Accounting; Address; Affect; Age; Aging; Agriculture; Algorithms; Alzheimer' s Disease; Alzheimer' s disease risk; Clinical; Cohort Studies; Consensus; Country; Data; Dementia; Environmental Exposure; Epidemiologic Studies; Equipment; Evaluation; Event; Exposure to; Frequencies; Funding; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Gold; Health; Hereditary Disease; High Prevalence; Home environment; Impaired cognition; Individual; Inflammation; Knowledge; Link; Longitudinal Studies; Metabolism; Methods; National Institute of Environmental Health Sciences; Neuraxis; Neurodegenerative Disorders; Organophosphates; Outcome; Participant; Pathway interactions; Peroxisome Proliferator-Activated Receptors; Pesticides; Population; Population Study; Prospective Studies; Public Health; Research; Risk Factors; Science; Telephone; Testing; age related cognitive disorder; base; clinical Diagnosis; disability; experience; genetic analysis; high risk; modifiable risk; organochlorine exposure; pesticide exposure; population based; prevent; prolyl-proline; public health relevance; risk variant; sample collection; screening; toxic organophosphate insecticide exposure

DESCRIPTION (provided by applicant): Both environmental and genetic components contribute to Alzheimer's disease (AD), but there has been limited research determining a link between exposure, genetics, and AD. One ubiquitous environmental exposure is pesticides, which affect the central nervous system and are associated with increased risk of AD in some studies. Current understanding of the association between pesticide exposure and AD is limited by knowledge gaps due to prior studies lacking detailed information on pesticide exposure, reliance on retrospective recall of exposure years after pesticide use, and lack of control for genes known to contribute to AD risk. We propose to address existing knowledge gaps in pesticide-related risks for AD by combining a proven method to identify individuals with AD, genetic sample collection, and detailed information on pesticide exposure in the Agricultural Health Study (AHS). We propose to identify AD cases beginning with telephone dementia screening of 4000 AHS participants, combined with an in-home evaluation of suspected cases and selected controls, leading to a consensus clinical diagnosis of AD and other dementias. Our rationale for the AHS is that it is the best-suited population study for examining pesticide exposure outcomes because it collected detailed information on pesticide use during or near the period of exposure, rather than retrospective estimates obtained years after potential exposure. A critical advantage to the AHS assessment approach is that it provides more accurate information on specific pesticide compounds, use of protective equipment, and mixing methods, leading to more advanced algorithms for estimating exposure. Because the AHS is an established longitudinal study, its well-characterized data can facilitate a prospective study of dementia that would otherwise take decades to complete if established de novo. We will leverage our research group's extensive experience and proven methods for AD case identification and genetic analysis in population-based studies. The unique strengths of the AHS and the project team make the current proposal exceptionally well- suited to address critical scientific questions posed by the Research Funding Announcement (RFA-ES-13- 006). Our Specific Aims are to 1) examine whether AD is associated with levels of pesticide exposure and types of pesticide use among pesticide applicators in the AHS, 2) examine the association between levels of pesticide exposure and AD after accounting for known AD genes and inflammation genes, and 3) examine the association between levels of pesticide exposure and AD, stratifying by genes known to alter metabolism of pesticides. Knowledge gained from the proposed research can be used to identify modifiable risk factors for AD and to develop strategies to reduce AD risk due to environmental exposures.

描述（由申请人提供）：环境和遗传成分都导致了阿尔茨海默氏病（AD），但是有限的研究决定了暴露，遗传学和AD之间的联系。一种无处不在的环境暴露是农药，这会影响中枢神经系统，并在某些研究中与AD风险增加有关。当前对农药暴露与AD之间关联的了解受到知识差距的限制，因为先前的研究缺乏有关农药暴露的详细信息，依赖农药使用后几年的暴露率以及对已知有助于AD风险的基因的控制。我们建议通过合并一种验证的方法来识别AD，遗传样本收集的人，以及有关农业健康研究（AHS）中有关农药暴露的详细信息，以解决与农药相关的AD风险的现有知识差距。我们建议确定从4000名AHS参与者的电话痴呆症筛查开始的AD病例，并结合对可疑病例和选定对照的家庭评估，从而导致对AD和其他痴呆症的共识临床诊断。我们对AHS的理由是，它是检查农药暴露成果的最适合人口研究，因为它收集了有关暴露期间或接近农药使用的详细信息，而不是潜在暴露后获得的年度回顾性估计值。 AHS评估方法的一个关键优势是，它提供了有关特定农药化合物，使用保护设备和混合方法的更准确的信息，从而导致更先进的算法来估计暴露。由于AHS是一项已建立的纵向研究，因此其特征性的数据可以促进对痴呆症的前瞻性研究，如果从头开始，则需要数十年的时间才能完成。我们将利用研究小组在基于人群的研究中的广泛经验和广泛的AD病例识别和遗传分析的方法。 AHS和项目团队的独特优势使当前的提案非常适合解决研究资金公告（RFA-ES-13- 006）提出的关键科学问题。我们的具体目的是1）检查AHS中农药施加器中农药的暴露水平以及农药使用的水平是否相关，2）检查在考虑到已知的AD基因和炎症基因和炎症基因之后的农药暴露水平与AD之间的关联，以及3）研究中已经知道的基因与已知的Meterabolism ofercoriss sernees sernes calleas sernes sernes callise cornebolism servicess prectiestece serne cornesebolism servicessives serne cornessives。从拟议的研究中获得的知识可用于确定AD的可修改风险因素，并制定因环境暴露而降低AD风险的策略。