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

Maitreyi Mazumdar, Weiming Xia, Oliver Hofmann, Matthew Gregas, Shannan Ho Sui, Winston Hide, Ting Yang, Herbert L. Needleman, David C. Bellinger

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)702-707
Number of pages6
JournalEnvironmental health perspectives
Volume120
Issue number5
DOIs
StatePublished - May 2012
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Children
  • Fetal basis of adult disease
  • Human
  • Lead

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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