LEAD-GENE INTERACTIONS AND CONGNITION

先导基因相互作用和认知

• 批准号: 7115197
• 负责人: Marc G Weisskopf
• 金额: $ 64.52万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-02-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115197
• 关键词: apolipoprotein E; biomarker; bone imaging /visualization /scanning; bone metabolism; clearance rate; clinical chemistry; clinical research; cognition disorders; creatinine; disease /disorder etiology; gene environment interaction; gene expression; genetic susceptibility; human old age (65+); human subject; hypertension; lead poisoning; longitudinal human study; neuropsychological tests; neurotoxicology; pathologic process; statistics /biometry; tau proteins; toxicant interaction; transferrin; urinalysis

DESCRIPTION: (provided by applicant) Cognitive decline is a common, but not inevitable, accompaniment to aging. While much research is currently being directed at Alzheimer' s Disease -- one of the most severe expressions of cognitive decline -- relatively little work is currently aimed at identifying risk factors and mechanisms associated with early (i.e., subclinical) cognitive decline, even though this may be the stage most amenable to prevention. An important issue that needs to be clarified in relation to the etiology of cognitive decline is the role of environmental lead exposure and the interaction of lead with specific candidate genes. In this application we discuss how four candidate genes -- APOE, the HFE (hemochromatosis) gene, transferrin, and Tau protein -- may interact with lead burden to increase the risk for oxidative cell damage leading to neuronal cell loss and cognitive deficits. We review the last 11 years of our research on low-level lead toxicity and describe compelling preliminary data. We then propose a new study that calls for new data collection in our established Bostonarea cohorts [Normative Aging Study (NAS), Nurses Health Study (NHS), and Community Lead Study (CLS)]. Our specific aims are to test hypotheses related to the impact on cognition of lead burden and its potential interaction with our four polymorphisms of interest. We will look at cognition cross-sectionally and longitudinally, using a validated battery of telephone cognitive function assessment tools as well as a battery of in-person cognitive tests that we have been administering in person since 1993. Results of this research promise to shed further light on lead's potential impact on society and may also give rise to tools for identifying susceptible individuals as well as early brain effects.

描述：（由申请人提供）认知能力下降是一种常见的，但不是不可避免的，伴随着衰老。虽然目前许多研究都是针对阿尔茨海默病--认知能力下降的最严重表现之一--但目前相对较少的工作是针对确定与早期（即，亚临床）认知衰退，即使这可能是最适合预防的阶段。一个重要的问题，需要澄清的认知能力下降的病因是环境铅暴露的作用和铅与特定的候选基因的相互作用。在这个应用程序中，我们讨论了四个候选基因-载脂蛋白E，HFE（血色素沉着症）基因，转铁蛋白和Tau蛋白-可能与铅负荷相互作用，以增加氧化细胞损伤的风险，导致神经元细胞损失和认知缺陷。 我们回顾了过去11年来对低水平铅毒性的研究，并描述了令人信服的初步数据。然后，我们提出了一项新的研究，要求在我们建立的波士顿地区队列中收集新的数据[规范性老龄化研究（NAS），护士健康研究（NHS）和社区领导研究（CLS）]。我们的具体目标是测试相关的假设铅负荷的认知和潜在的相互作用与我们的四个多态性的利益的影响。我们将使用一组经过验证的电话认知功能评估工具以及一组我们自1993年以来一直亲自进行的认知测试，从横截面和纵向上研究认知。这项研究的结果有望进一步阐明铅对社会的潜在影响，也可能产生识别易感个体和早期大脑影响的工具。