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Environ Health Perspect. 2012 May;120(5):702-7. doi: 10.1289/ehp.1104474. Epub 2012 Feb 7.

Prenatal lead levels, plasma amyloid β levels, and gene expression in young adulthood.

Author information

1
Department of Neurology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. maitreyi.mazumdar@childrens.harvard.edu

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.

PMID:
22313790
PMCID:
PMC3346789
DOI:
10.1289/ehp.1104474
[Indexed for MEDLINE]
Free PMC Article

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