APOE and Alzheimer disease: However, considering that the insular cortex is often involved in AD (Bonthius et al., 2005) and the lower gyrification index in AD (Im et al., 2008; King et al., 2010), it should be noted that the APOE genotype may affect the HDLC-Aβ interaction, which would result in the decreased gyrification of insular and frontal opercular cortex.