APOE and Alzheimer disease: Compared with APOE3, the APOE4 isoform increases AD risk and theAPOE2 isoform reduces AD risk.166 A single amino acid difference between APOE3 and APOE4 leads to the changing of protein conformation which affects the binding of APOE with its receptors, lipids, and Aβ.167 Carrying one APOE4 allele increases the risk of AD by 3–4 times, and carrying two alleles increases the risk by 9–15 times.168 APOE4 isoform may affects the development and progression of AD through multiple different pathways in which inflammatory regulation plays crucial role.166