Translational potential of JAX humanized‐APOE mice model: Accelerated midlife endocrine aging in hAPOEε4/4 females

Age, female sex and APOEε4 genotype are the greatest Alzheimer’s (AD) risk factors, with a stronger APOEε4 link to AD in women. The APOE‐sex interaction is also evident in hAPOE mouse models where APOEε4 induces more severe neurodegeneration and cognitive deficits in female mice. However, the mechanisms by which these two risk factors converge to disrupt brain function remain elusive.