Figure 2.

Sex differences in penetrance, symptom onset, and biomarker progression in Alzheimer’s disease (AD) across genetically determined AD populations. This figure illustrates the near-full penetrance of AD in autosomal dominant Alzheimer’s disease (ADAD), Down syndrome-associated AD (DSAD), and APOE44 carriers, alongside the predictable sequence of AD biomarker changes (amyloid deposition, tau accumulation, and neurodegeneration). No significant sex differences were observed in most aspects of penetrance, symptom onset, or biomarker progression. However, notable exceptions include increased cortical thinning and reduced hippocampal and amygdala volumes in female ADAD carriers compared to males. Additionally, earlier decreases in Aβ42 levels were reported in APOE44 males, while greater cortical thickness was observed in APOE44 females. Conflicting findings were noted in DSAD for penetrance and symptom onset, with larger recent studies reporting no significant sex differences.