Based on our data, the increased female susceptibility to Alzheimer’s disease in the carriers of ACE mutation R1279Q may be due to direct structural differences between male and female brain ACE (i.e., due to differences in glycosylation of male and female ACE), or indirectly due to functional differences in male and female brain ACE caused by differential interactions with putative ACE-binding proteins (or substrates) that result from structurally different male and female ACE in the brains of patients with this mutation. This evidence concerns the gene ACE and Alzheimer disease.