APOE and Alzheimer disease: In contrast, another study with 117 participants with AD, including 21 APOE4 homozygotes, found a sex-specific response to APOE4 dosage: males required two copies of the allele to reach tau levels that females achieved with just one, suggesting higher susceptibility in females to the effects of APOE4 on tau pathology (Yan et al., 2021).