Abstract:
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.
journal_name
Environ Health Perspectjournal_title
Environmental health perspectivesauthors
Mazumdar M,Xia W,Hofmann O,Gregas M,Ho Sui S,Hide W,Yang T,Needleman HL,Bellinger DCdoi
10.1289/ehp.1104474subject
Has Abstractpub_date
2012-05-01 00:00:00pages
702-7issue
5eissn
0091-6765issn
1552-9924journal_volume
120pub_type
杂志文章abstract:BACKGROUND:Benzene is a common industrial chemical known to induce leukemia and other blood disorders, as well as aneuploidy, in both human blood cells and sperm at exposures > 10 ppm. Recent reports have identified health effects at exposure levels < 1 ppm, the permissible exposure limit (PEL; 8 hr) set by the U.S. Oc...
journal_title:Environmental health perspectives
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journal_title:Environmental health perspectives
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更新日期:1990-04-01 00:00:00
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journal_title:Environmental health perspectives
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