By analyzing data from the FHS and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), for the first time, at the genome-wide significance level (p < 5.0×10− 8) we found that elevated blood MCP-1 increased AD risk, hippocampal atrophy, and AD neuropathology only in people carrying one genotype of SNPs in two gene loci: Neuron navigator 3 (NAV3 rs696468) and Unc-5 Netrin Receptor C (UNC5C rs72659964). This evidence concerns the gene NAV3 and hippocampal atrophy.