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

早年和晚年的金属暴露与阿尔茨海默病

• 批准号: 9511526
• 负责人: Marc G Weisskopf
• 金额: $ 86.36万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-11 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9511526
• 关键词: Ablation; Address; Adult; Affect; Aluminum; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid beta-Protein; Animal Experimentation; Area; Attention; Autopsy; Biological Markers; Blood; Blood specimen; Brain; Case-Control Studies; Childhood; Clinical; Cohort Studies; Dental Care; Dental Clinics; Dental Enamel; Development; Elderly; Epidemiology; Fluorescence; Gold; Health; Human; Inductively Coupled Plasma Mass Spectrometry; Ions; Lasers; Lead; Life; Literature; Massachusetts; Measurement; Measures; Medical Records; Medical center; Metal exposure; Metals; Methodology; Nail plate; Outcome; Pathogenesis; Pathology; Patients; Persons; Physiological; Plasma; Population; Preventive; Proteins; Research; Risk; Roentgen Rays; Role; Sampling; Secondary Dentin; Site; Source; Suggestion; Techniques; Temporal Lobe; Testing; Time; Tissues; Tooth structure; Urine; Veterans; Visit; Work; bone; brain tissue; case control; cognitive function; drinking water; early life exposure; epidemiology study; experience; lead concentration; lead exposure; non-demented; public health relevance; recruit

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.

描述（由申请人提供）：我们建议研究早年和成年时期接触金属与患阿尔茨海默病 (AD) 的风险之间的关系，以及这些接触是否与淀粉样蛋白水平的变化相关。我们将对来自伊迪丝·诺尔斯·罗杰斯纪念贝德福德 VA 医疗中心 (Bedford VA) 的约 183 名病例和 270 名对照进行一项病例对照研究。此外，我们建议另外检查早期和晚年的金属暴露是否与对照组认知功能较差有关，贝德福德 VA 提供了一个独特的适合开展这项研究的环境，因为该机构为 AD 患者提供服务，并设有牙科诊所。 -我们可以从中招募适当的对照并提供牙齿样本，病例和对照的来源人群都是马萨诸塞州贝德福德地区的退伍军人。此外，基本上所有临床 AD 病例都会进行尸检，因此可以确认病例状态。神经病理学和脑组织可以收集用于分析的早期生命接触金属的情况将通过测量成人牙釉质中的金属来评估（使用激光烧蚀电感耦合等离子体质谱法）。对照者将在拔牙用于其他目的时从贝德福德 VA 牙科诊所招募。如果患者在世时因其他原因拔牙，则将从病例中收集牙齿，或者 尸检时，还将使用非侵入性 K 壳 X 射线荧光 (KXRF) 技术来测量成人的铅 (Pb) 暴露量，我们过去曾使用该技术在研究访视时收集的血液样本中测量 Aβ 种类。尸检时收集的颞叶皮层脑组织将在研究访问时对对照组进行测试。这项研究将是第一个使用暴露生物标志物来研究成人接触金属与 AD 之间关系的研究。去探索生命早期金属暴露与人类阿尔茨海默病之间的关联——动物研究中提出的关于铅暴露的假设，但在没有牙齿可以提供的早期暴露生物标志物的情况下，基本上无法在人类中进行测试。