APOE DNA methylation is altered in Lewy body dementia

Abstract

<div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d8865824e317">INTRODUCTION</h5> <p id="P1">Inheritance of the ε4 allele of apolipoprotein E ( <i>APOE</i>) increases a person’s risk of developing both Alzheimer’s disease (AD) and Lewy body dementia (LBD), yet the underlying mechanisms behind this risk are incompletely understood. The recent identification of reduced <i>APOE</i> DNA methylation in AD postmortem brain (PMB) prompted this study to investigate <i>APOE</i> methylation in LBD. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d8865824e331">METHODS</h5> <p id="P2">Genomic DNA from PMB tissues (frontal lobe and cerebellum) of neuropathological pure (np) Controls, npAD, LBD + AD, and npLBD subjects were bisulfite pyrosequenced. DNA methylation levels of two <i>APOE</i> subregions were then compared for these groups. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d8865824e339">RESULTS</h5> <p id="P3"> <i>APOE</i> DNA methylation was significantly reduced in npLBD compared to npControls, and methylation levels were lowest in the LBD + AD group. </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d8865824e347">DISCUSSION</h5> <p id="P4">Given that npLBD and npAD PMB shared a similar reduction in <i>APOE</i> methylation, it is possible that an aberrant epigenetic change in <i>APOE</i> is linked to risk for both diseases. </p> </div>