Prenatal lead levels, plasma amyloid β levels, and gene expression in young adulthood.
Prenatal lead levels, plasma amyloid β levels, and gene expression in young adulthood.
复制标题
DOI：
10.1289/ehp.1104474
复制
发表时间：
2012-05
影响因子：
10.4
通讯作者：
Bellinger DC
中科院分区：
文献类型：
--
作者：
Mazumdar M;Xia W;Hofmann O;Gregas M;Ho Sui S;Hide W;Yang T;Needleman HL;Bellinger DC
背景：动物研究表明，早期铅暴露会影响基因表达和与阿尔茨海默氏病（AD）相关的蛋白质的产生。
目标：我们试图评估年轻男性和女性的早期生命铅暴露与潜在的AD生物标志物之间的关系。
方法：我们使用三明治酶连接的免疫吸附测定法（ELISA）来测量55名在前瞻性研究中，淀粉样蛋白β蛋白Aβ40和Aβ42的血浆浓度在55名成年人中参与了前瞻性研究，以期待铅的效果。
结果：在13位脐带血铅浓度（≥10μg/dl）的参与者中，平均血浆Aβ42浓度低于42名脐带血铅浓度较低的参与者（p = 0.08） （RTN4）和低密度脂蛋白受体相关蛋白相关的蛋白质1（LRPAP1）基因，其产物被认为会影响Aβ的产生和沉积。
结论：我们的探索性研究的数据表明，产前铅暴露可能会影响Aβ相关的生物学途径，这些途径已在AD发作中暗示。
Background: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer’s disease (AD). Objectives: We attempted to assess the relationship between early-life lead exposure and potential biomarkers for AD among young men and women. We also attempted to assess whether early-life lead exposure was associated with changes in expression of AD-related genes. Methods: We used sandwich enzyme-linked immunosorbent assays (ELISA) to measure plasma concentrations of amyloid β proteins Aβ40 and Aβ42 among 55 adults who had participated as newborns and young children in a prospective cohort study of the effects of lead exposure on development. We used RNA microarray techniques to analyze gene expression. Results: Mean plasma Aβ42 concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (≥ 10 μg/dL) than in 42 participants with lower cord blood lead concentrations (p = 0.08). Among 10 participants with high prenatal lead exposure, we found evidence of an inverse relationship between umbilical cord lead concentration and expression of ADAM metallopeptidase domain 9 (ADAM9), reticulon 4 (RTN4), and low-density lipoprotein receptor-related protein associated protein 1 (LRPAP1) genes, whose products are believed to affect Aβ production and deposition. Gene network analysis suggested enrichment in gene sets involved in nerve growth and general cell development. Conclusions: Data from our exploratory study suggest that prenatal lead exposure may influence Aβ-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.
登录
查看更多内容
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
5.8
作者：
MacArthur, Ben D.;Lachmann, Alexander;Ma'ayan, Avi
通讯作者：
Ma'ayan, Avi
影响因子：
2.5
作者：
Giedraitis, Vilmantas;Sundelof, Johan;Lannfelt, Lars
通讯作者：
Lannfelt, Lars
影响因子：
15.8
作者：
Ioannidis, JPA
通讯作者：
Ioannidis, JPA
影响因子：
9.9
作者：
COBB, JL;WOLF, PA;DAGOSTINO, RB
通讯作者：
DAGOSTINO, RB