APOE and Alzheimer disease: In addition to APOE, over 20 risk loci have been identified in genome-wide association studies of late-onset AD or dementia, which are related to immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein metabolism, showing the genetic and pathophysiological complexity of the disease and also highlighting the importance of comorbid or pleiotropic associations, gender differences, maternal history, and epigenetic factors (22).