This study aims to investigate the mechanisms by which apolipoprotein E (APOE) genotype modulates the relationship between low‐density lipoprotein receptor‐related protein 1 (LRP1) rs1799986 variant on the default mode network (DMN) and cognition in Alzheimer's disease (AD) spectrum populations. The gene discussed is LRP1; the disease is early-onset autosomal dominant Alzheimer disease.