In addition to characterizing the impact of risk genes on brain imaging phenotypes of AD [51], we recently found that individuals with a maternal family history of AD have reductions in gray matter volume in AD-vulnerable brain regions at baseline, and that these same healthy individuals have progressive gray matter volume reductions in select AD-vulnerable brain regions over two years, independent of APOE ε4 status [5], [52]. This evidence concerns the gene APOE and Alzheimer disease.