In line with the findings by Lowe et al. [5] who showed that most of the APOE4-related differences in hypometabolism are mediated by amyloid accumulation, hypometabolism associated with APOE4 or FH in the AD signature regions in the current sample was only observed in individuals with high Aβ deposition (Additional file 1: Figure S1, Table S5), suggesting that the effects of APOE4 or FH on cerebral glucose metabolism only begin to show when the disease is progressed. This evidence concerns the gene FH and Alzheimer disease.