The impact of the APOE4 allele on cholesterol and low-density lipoprotein metabolism is significantly altered in female Alzheimer's disease patients, but not in males.72 Modulations of endogenous sex hormones,73 particularly after menopause, may amplify the detrimental impact of APOE4 in females due to the loss of oestrogen's protective effects.74 The absence of significant changes between WM and the DMN among males with the APOE4 allele could further support the hypothesis of a relative resistance to the effects of the APOE4 gene in males. The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.