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 Alzheimer's disease (AD).


OBJECTIVE
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.
Department of Neurology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. maitreyi.mazumdar@childrens.harvard.edu
Maitreyi
M
Mazumdar
Weiming
W
Xia
Oliver
O
Hofmann
Matthew
M
Gregas
Shannan
S
Ho Sui
Winston
W
Hide
Ting
T
Yang
Herbert L
HL
Needleman
David C
DC
Bellinger
D000328:Adult; D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D006801:Humans; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D007854:Lead