APOE ε4 and risk for Alzheimer's disease: Do regionally distributed white matter hyperintensities play a role?

Abstract Background We previously demonstrated that parietal lobe white matter hyperintensities (WMH) increase the risk for Alzheimer's disease (AD). Here, we examined whether individuals with apolipoprotein E gene ( APOE ε4) have increased parietal WMH volume. Methods Participants were from the Washington Heights-Inwood Columbia Aging Project (WHICAP; n = 694, 47 with dementia) in northern Manhattan and the Etude Santé Psychologique Prévalence Risques et Traitement study (ESPRIT; n = 539, 8 with dementia) in Montpellier. The association between regional WMH and APOE ε4 was examined separately in each group and then in a combined analysis. Results In WHICAP, ε4 carriers had higher WMH volume particularly in parietal and occipital lobes. In ESPRIT, ε4 carriers had elevated WMH particularly in parietal and temporal lobes. In the combined analysis, ε4 carriers had higher WMH in parietal and occipital lobes. Increased WMH volume was associated with increased frequency of dementia irrespective of APOE ε4 status; those with the ε4 were more likely to have dementia if they also had increased parietal WMH. Conclusions APOE ε4 is associated with increased parietal lobe WMH.