APOE4 expression is associated with impaired autophagy and mitophagy in astrocytes

Among the risk factors for late onset sporadic Alzheimer's disease(AD)is the expression ofε4 allele of apolipoprotein E(APOE4)gene(Mahley et al.,2006).Elevated amyloid processing and reduced degradation of Aβ,which lead to Ap plaque deposition,are evident in APOE4-positive AD patients and mice(Mahley et al.,2006).These features correlate with neuronal cell loss.Impaired mitochondrial activity and increased oxidative stress have long been recognized as additional hallmarks of AD pathology(Mahley et al.,2006).The effect of APOE4 expression on autophagy and mitochondrial dynamics and activity in astrocytes is discussed in this perspective and is summarized in Figure 1.