INS and Alzheimer disease: Thus, carrying APOE4 isoform may impair the lipid transport and disrupt the lipid homeostasis in the brain, inducing chronic inflammation and subsequently lead to neurodegeneration.170 The brain is also a highly energy-demanding organ, dysfunction of brain glucose metabolism is another risk factor for AD development.171 Mounting in vitro and in vivo evidences have demonstrated that APOE4 can inhibit insulin signaling and decrease glucose usage in the brain through multiple mechanisms,172–174 this might be another way APOE4 induces neuroinflammation and promotes the development of AD.