title: Infantile exposure to lead and late-age cognitive decline: relevance to AD.
abstract: BACKGROUND
  Early-life lead (Pb) exposure induces overexpression of the amyloid beta precursor protein and its amyloid beta product in older rats and primates. We exposed rodents to Pb during different life span periods and examined cognitive function in old age and its impact on biomarkers associated with Alzheimer's disease (AD).
  
  
  METHODS
  Morris, Y, and the elevated plus mazes were used. Western blot, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay were used to study the levels of AD biomarkers.
  
  
  RESULTS
  Cognitive impairment was observed in mice exposed as infants but not as adults. Overexpression of AD-related genes (amyloid beta precursor protein and β-site amyloid precursor protein cleaving enzyme 1) and their products, as well as their transcriptional regulator-specificity protein 1 (Sp1)-occurred only in older mice with developmental exposure to Pb.
  
  
  CONCLUSIONS
  A window of vulnerability to Pb neurotoxicity exists in the developing brain that can influence AD pathogenesis and cognitive decline in old age.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
authors.forename: Syed Waseem
authors.initials: SW
authors.lastname: Bihaqi
authors.affiliation: Interdisciplinary Neuroscience Program (INP), University of Rhode Island, Kingston, RI, USA.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Bahmani
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA.
authors.forename: Gehad M
authors.initials: GM
authors.lastname: Subaiea
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA; Interdisciplinary Neuroscience Program (INP), University of Rhode Island, Kingston, RI, USA. Electronic address: nzawia@uri.edu.
authors.forename: Nasser H
authors.initials: NH
authors.lastname: Zawia
mesh_terms: D000375:Aging; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D023181:Antimicrobial Cationic Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C585481:arginyl-lysyl-lysyl-arginyl-leucyl-lysyl-leucyl-leucyl-lysyl-arginyl-leucyl-leucinamide; D007854:Lead; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Aging; Alzheimer's disease; Cognition; Development; Lead; Life span