However, APOE4 expression has also been shown to have deleterious effects on numerous Aβ-independent pathways, including lipid metabolism, tau pathology, bioenergetics, neuronal development, synaptic plasticity, the neuro-vasculature, and neuro-inflammation [see reviews by14 and15], any number of which could play an important role in the pathogenesis of AD among APOE4 carriers. Here, APOE is linked to Alzheimer disease.