APOE and early-onset autosomal dominant Alzheimer disease: Several studies have identified age, sex and the apolipoprotein E allele 4 (APOE4) gene as significant risk factors for memory loss.3,4 As the strongest genetic risk factor for Alzheimer's disease,5  APOE4 contributes to accelerated brain changes decades before clinical symptoms emerge, including grey matter (GM) atrophy and synaptic dysfunction.4,6 Notably, these effects are sex-dependent.