OPRK1 and Alzheimer disease: A 2016 systematic review by Wen et al. described studies reporting higher methylation levels of several genes (observed in peripheral blood cells or brain tissue of AD patients) including OPRK1, BDNF, UQCRC1, HTERT, TREM2, TBX2AR, SORBS3, SPTBN4, and CREB promotors and the synaptophysin gene [30].