Alzheimer's disease -like pathology in aged monkeys after infantile exposure to environmental metal lead : evidence for a developmental origin and environmental link for AD

J Neurosci 28:3-9 (2008)
  Copy   BIBTEX


The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD



    Upload a copy of this work     Papers currently archived: 92,907

External links

Setup an account with your affiliations in order to access resources via your University's proxy server

Through your library

Similar books and articles


Added to PP

156 (#124,846)

6 months
111 (#40,713)

Historical graph of downloads
How can I increase my downloads?

Author Profiles

John Harry
Adam Mickiewicz University
Bryan Maloney
Indiana University Purdue University, Indianapolis

References found in this work

No references found.

Add more references