Involvement of 5-lipoxygenase in Alzheimer's disease: a role for DNA methylation.

Lipoxygenases play a major role in the neuropathology of Alzheimer's disease (AD), even though the underlying mechanisms are as yet poorly understood. Here, we studied the epigenetic regulation of 5-lipoxygenase (5-LOX) in peripheral blood mononuclear cells of subjects with late-onset AD and age-matched controls. We found a significant increase in 5-LOX gene expression in AD subjects compared to healthy controls, paralleled by increased 5-LOX protein and leukotriene B4, the 5-LOX product. In addition, a consistent reduction in DNA methylation at 5-LOX gene promoter was documented in AD versus healthy subjects. Taken together, our findings further support a role for 5-LOX in vulnerability to neurodegeneration.