In the brain, cholesterol is synthesized in astrocytes and transported to neurons with the cholesterol transport protein apolipoprotein E (apoE). The cholesterol controls the clustering of amyloid precursor protein with gamma secretase in GM1 lipid domains. High cholesterol induces APP hydrolysis and the eventual accumulation of amyloid plaques tau phosphorylation. The ApoE isotype4 is the greatest risk factor for sporadic Alzheimer's and this allele was shown to increase cholesterol in mice.