Although we cannot exclude a significant role of such pathways in our observations, we did not observe that mRNA levels of BACE1, neprilysin, and IDE were significantly altered by either the simple or interactive effects of Western diet and APOE. Another compelling candidate mechanism is neuroinflammation, which is widely implicated as a significant regulator of AD risk and development of AD pathology (Glass et al., 2010; Wyss-Coray and Rogers, 2012; Heneka et al., 2015). This evidence concerns the gene MME and Alzheimer disease.