Affiliations: [a] Department of Biomedical Sciences, University of Teramo, Teramo, Italy | [b] Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy | [c] Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy | [d] European Center for Brain Research/IRCCS Santa Lucia Foundation, Rome, Italy | [e] Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy
Correspondence:
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Correspondence to: Claudio D'Addario, Department of Biomedical Sciences, University of Teramo, Teramo, Italy. Tel./Fax: +39 0861 266877; E-mail: [email protected] or Mauro Maccarrone, Center of Integrated Research, Campus Bio-Medico University of Rome, Rome, Italy. Tel./Fax: +39 06 2254 19169; E-mail: [email protected].
Abstract: 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.
