White matter hyperintensities are associated with amyloid burden in APOE4 non-carriers

Young Noh, Sang Won Seo, Seun Jeon, Jong Min Lee, Jung Hyun Kim, Geon Ha Kim, Hanna Cho, Cindy W. Yoon, Hee Jin Kim, Byoung Seok Ye, Sung Tae Kim, Yearn Seong Choe, Kyung Han Lee, Jae Seung Kim, Michael Ewers, Michael W. Weiner, Jae Hong Lee, David J. Werring, Dae Ryong Kang, Chang Soo KimDuk L. Na

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33 Scopus citations


Previous preclinical studies have suggested a close relationship between cerebrovascular disease (CVD) and Alzheimer's disease. However, a direct correlation between CVD and amyloid burden has not yet been shown in humans. If there is a relationship between CVD and amyloid burden, it is possible that the apolipoprotein E4 (APOE4) genotype may have an effect on this relationship because APOE4 is a risk factor for the development of AD. We therefore evaluated the effects of APOE4 on the relationship between white matter hyperintensities (WMH), a marker of CVD, and amyloid burden, measured by 11C- Pittsburgh compound B (PiB) PET. We recruited 53 patients with subcortical vascular cognitive impairments, who had both WMH on MRI and amyloid deposition assessed by PiB PET. Twenty-two of these patients were APOE4 carriers (41.5%). In the APOE4 non-carriers, a significant positive correlation was shown between the volume of WMH and PiB retention (β = 7.0 × 10-3, p = 0.034) while no significant correlation was found in APOE4 carriers (β = -9.0 × 10-3, p = 0.085). Statistical parametric mapping analyses in APOE4 non-carriers showed that WMH were associated with PiB retention in the bilateral medial occipitotemporal gyrus, cuneus, and superior cerebellum. Our results suggested that WMH are correlated with amyloid burden especially in the posterior brain regions in APOE4 non-carriers. However, this correlation was not observed in APOE4 carriers, perhaps because in these subjects the influence of APOE4 overrides the effect of CVD.

Original languageEnglish
Pages (from-to)877-886
Number of pages10
JournalJournal of Alzheimer's Disease
Issue number4
StatePublished - 2014


  • Alzheimer's disease
  • amyloid burden
  • apolipoprotein E4
  • cerebrovascular disease


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