APOE and early-onset autosomal dominant Alzheimer disease: Prior research indicates that APOE4 carriers exhibit distinct inflammatory and metabolic responses based on sex, with women generally showing greater susceptibility to tau pathology, along with neuroinflammation and metabolic dysfunction.41, 42, 43 This may explain why APOE4 has been linked to a higher risk of Alzheimer’s disease in women, particularly postmenopausal, when oestrogen—known for its neuroprotective and anti-inflammatory effects—declines.44