Early and late-life metal exposures and Alzheimer's disease

描述（由申请人提供）：我们建议研究早期和成年时期接触金属与患阿尔茨海默病（AD）风险之间的关系，以及这些接触是否与血液和大脑中淀粉样蛋白-β物种（Aβ）水平的变化有关。我们将进行一项病例对照研究，从伊迪丝·诺斯·罗杰斯纪念贝德福德VA医疗中心（Bedford VA）招募约183例病例和270例对照。此外，我们建议进一步研究早期和后期生活中的金属暴露是否与对照组的认知功能恶化有关。贝德福德退伍军人医院提供了一个独特的适合进行这项研究的环境，因为该机构为阿尔茨海默病患者提供服务，并有一个牙科诊所，我们可以从那里招募适当的对照者，并提供牙齿样本。病例和对照的源人群都是马萨诸塞州贝德福德地区的退伍军人。此外，基本上所有的临床AD病例都要经过尸检，因此可以从神经病理学上确认病例状态，并收集脑组织进行分析。通过测量成年牙釉质中的金属（使用激光消融电感耦合等离子体质谱法）来评估早期接触金属的情况。对照者将从贝德福德VA牙科诊所招募，当他们因其他原因拔牙时，他们的牙齿将从他们活着时因其他原因拔牙的病例中收集，或者

DESCRIPTION (provided by applicant): We propose to study the relation between exposure to metals-in both early life and adult life-and the risk of developing Alzheimer's disease (AD), and whether those exposures are associated with changes in levels of amyloid-β species (Aβ) in blood and brain. We will conduct a case-control study with an estimated 183 cases and 270 controls recruited from the Edith Nourse Rogers Memorial Bedford VA Medical Center (Bedford VA). Furthermore, we propose to additionally examine whether early and later life metal exposures are associated with worse cognitive function among the controls. The Bedford VA provides a uniquely suited setting in which to conduct this research as the facility serves AD patients and has a dental clinic on-site from which we can recruit appropriate controls with availability of tooth samples. The source population for both cases and controls are veterans in the Bedford, MA area. In addition, essentially all clinical AD cases go to autopsy, thus case status can be confirmed neuropathologically and brain tissue can be collected for analyses. Early life exposure to metals will be assessed by measuring metals in adult tooth enamel (using laser-ablation inductively coupled plasma mass spectrometry). Controls will be recruited from the Bedford VA dental clinic when they are having a tooth extracted for other reasons, and teeth will be collected from cases if they are having a tooth extracted for other reasons while alive, or at autopsy. Adult exposure to lead (Pb) will also be measured with the non-invasive K-shell X-ray Fluorescence (KXRF) technique with which we have extensive past experience. Aβ species will be measured in blood samples collected at study visits and temporal cortex brain tissue collected at autopsy. Cognitive function will be tested among the controls at their study visit. This study will be the first to examine the association between adult exposure to metals and AD using biomarkers of exposure, and the first of any kind to explore the association between early life metal exposures and AD in humans-a hypothesis suggested for Pb exposure from animal research, but essentially untestable in humans without the biomarker of such early exposure that teeth can provide.