Super-resolution imaging in the mouse brain shows that APOE utilizes astrocyte-derived cholesterol to specifically transport neuronal APP into and out of lipid clusters, and when cholesterol synthesis in astrocytes is reduced, APP effluent lipid clusters that interact with α-secretase to generate soluble APP-α (sAPP-α) potently reduce Aβ and Tau burden in AD mouse models [115]. Here, APP is linked to Alzheimer disease.