Increased β-amyloid deposition in Tg-SWDI transgenic mouse brain following in vivo lead exposure

Previous studies in humans and animals have suggested a possible association between lead (Pb) exposure and the etiology of Alzheimer's disease (AD). Animals acutely exposed to Pb display an over-expressed amyloid precursor protein (APP) and the ensuing accumulation of beta-amyloid (A beta) in brain extracellular spaces. This study was designed to examine whether in vivo Pb exposure increased brain concentrations of A beta, resulting in amyloid plaque deposition in brain tissues. Human Tg-SWDI APP transgenic mice, which genetically over-express amyloid plaques at age of 2-3 months, received oral gavages of 50 mg/kg Pb acetate once daily for 6 weeks: a control group of the same mouse strain received the same molar concentration of Na acetate. ELISA results revealed a significant increase of A beta in the CSF, brain cortex and hippocampus. Immunohistochemistry displayed a detectable increase of amyloid plaques in brains of Pb-exposed animals. Neurobehavioral test using Morris water maze showed an impaired spatial learning ability in Pb-treated mice, but not in C57BL/6 wild type mice with the same age. In vitro studies further uncovered that Pb facilitated A beta fibril formation. Moreover, the synchrotron X-ray fluorescent studies demonstrated a high level of Pb present in amyloid plaques in mice exposed to Pb in vivo. Taken together, these data indicate that Pb exposure with ensuing elevated A beta level in mouse brains appears to be associated with the amyloid plaques formation. Pb apparently facilitates A beta fibril formation and participates in deposition of amyloid plaques. (C) 2012 Elsevier Ireland Ltd. All rights reserved.