At baseline, average HP volume for NC (7,438 mm3) significantly differed from AD (6,310 mm3).In AD, baseline levels of VILIP-1, tau, and p-tau predicted whole-brain and HP atrophy.Cognitively NC subjects with CSF markers in the upper tercile had higher rates of whole-brain and HP atrophy compared to those with lower levels (adjusting for age, sex, imaging system type, and APOE ε4 genotype). CSF biomarker levels and rates of whole-brain and regional atrophy in this subset of controls were similar to AD subjects. This evidence concerns the gene APOE and Alzheimer disease.