Prenatal Lead Levels, Plasma Amyloid β Levels, and Gene Expression in Young Adulthood.

Background: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimerfs disease (AD). Objectives: We attempted to assess the relationship between early-life lead exposure and potential biomarkers for AD among young men and wo...

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Publicado en:Environmental Health Perspectives Vol. 120; no. 5; pp. 702 - 708
Autores principales: Mazumdar, Maitreyi, Xia, Weiming, Hofmann, Oliver, Gregas, Matthew, Sui, Shannan Ho, Hide, Winston, Yang, Ting, Needleman, Herbert L., Bellinger, David C.
Formato: research tables/charts Journal Article
Publicado: National Institute of Environmental Health Sciences May2012
Acceso en línea:Ver este registro en EBSCOhost
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      dt: May2012
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        atl: Prenatal Lead Levels, Plasma Amyloid β Levels, and Gene Expression in Young Adulthood.
      aug:
        au:
          Mazumdar, Maitreyi
          Xia, Weiming
          Hofmann, Oliver
          Gregas, Matthew
          Sui, Shannan Ho
          Hide, Winston
          Yang, Ting
          Needleman, Herbert L.
          Bellinger, David C.
        affil: Department of Neurology, Children's Hospital Boston, Boston, Massachusetts, USA; Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
      sug:
        subj:
          Gene Expression In Adulthood
          Lead Adverse Effects
          Environmental Exposure Adverse Effects
          Biological Markers
          Alzheimer's Disease Familial and Genetic
          Proteins Blood
          Prospective Studies
          Fetal Blood Analysis
          Exploratory Research
          Fetus
          Fetal Development
          Infant, Newborn
          Infant
          Child
          Child, Preschool
          Human
          Male
          Female
          Lead Blood
          Spectrum Analysis
          Questionnaires
          Enzyme-Linked Immunosorbent Assay
          RNA Blood
          Linear Regression
          Databases
          Descriptive Statistics
          Adult
          Funding Source
          Fetus, conception to birth
          Infant, Newborn: birth-1 month
          Infant: 1-23 months
          Child: 6-12 years
          Child, Preschool: 2-5 years
          Adult: 19-44 years
          Male
          Female
      ab: Background: Animal studies suggest that early-life lead exposure influences gene expression and production of proteins associated with Alzheimerfs 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.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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