The APOE-4, a major genetic risk factor for sporadic AD, has been found to affect gray matter and white matter structure as well as cortical rhythms and functional/structural connectivity in healthy subjects long before the onset of clinical dementia [29]–[32]. Likewise, subjects carrying the APOE-4 allele who already developed AD also have abnormal patterns of cortical oscillations compared with noncarriers [33], [34]. However, limited work has suggested that APOE genotype may modulate disease phenotype, in terms of brain functional connectivity [21], [35], and it is unclear whether the effects of APOE-4 on brain connectivity change throughout the stages of the disorder.
