Dataset Information

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

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 ? proteins A?40 and A?42 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 A?42 concentrations were lower among 13 participants with high umbilical cord blood lead concentrations (? 10 ?g/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 A? 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 A?-related biological pathways that have been implicated in AD onset. Gene network analysis identified further candidates to study the mechanisms of developmental lead neurotoxicity.

SUBMITTER: Mazumdar M

PROVIDER: S-EPMC3346789 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Publications

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

Mazumdar Maitreyi M Xia Weiming W Hofmann Oliver O Gregas Matthew M Ho Sui Shannan S Hide Winston W Yang Ting T Needleman Herbert L HL Bellinger David C DC

Environmental health perspectives 20120207 5

<h4>Background</h4>Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimer's disease (AD).<h4>Objectives</h4>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.<h4>Methods</h4>We used sandwich enzyme-linked immunosorben ...[more]

PMID: 22313790

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