APP and Alzheimer disease: The authors observed that lead exposure during brain development of rats and monkeys inhibits DNA-methyltransferases, thus resulting in hypomethylation of the promoters of genes associated with AD, such as APP. Whereas AD-related genes were over-expressed late in life, others were repressed, suggesting that early life perturbations result in hypomethylation of some genes as well as hypermethylation of others [144-146].