Elevated plasma BACE1 levels are associated with cerebral accumulation of Aβ, cognitive decline, atrophy in the basal forebrain and hippocampus, as well as decreased glucose metabolism in cognitively healthy individuals at risk for AD. BACE1 variant and APOE ε4 interaction have a role in brain Aβ deposition. This evidence concerns the gene APOE and Alzheimer disease.