White Matter Hyperintensities are associated with Amyloid Burden in APOE4 Non-Carriers

Article type: Research Article

Authors: Noh, Young^a | Seo, Sang Won^{b; *} | Jeon, Seun^c | Lee, Jong Min^c | Kim, Jung-Hyun^b | Kim, Geon Ha^d | Cho, Hanna^{b; e} | Yoon, Cindy W.^f | Kim, Hee Jin^b | Ye, Byoung Seok^{b; g} | Kim, Sung Tae^h | Choe, Yearn Seongⁱ | Lee, Kyung-Hanⁱ | Kim, Jae Seung^j | Ewers, Michael^k | Weiner, Michael W.^{l; m} | Lee, Jae-Hongⁿ | Werring, David J.^o | Kang, Dae Ryong^p | Kim, Chang Soo^q | Na, Duk L.^b

Affiliations: [a] Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea | [b] Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [c] Department of Biomedical Engineering, Hanyang University, Seoul, Korea | [d] Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea | [e] Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea | [f] Department of Neurology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea | [g] Department of Neurology, Yonsei University College of Medicine, Seoul, Korea | [h] Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [i] Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea | [j] Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea | [k] Institute for Stroke and Dementia Research, Ludwig-Maximilians-University, Munich, Germany | [l] University of California, San Francisco, San Francisco, CA, USA | [m] Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, SanFrancisco, CA, USA | [n] Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea | [o] Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK | [p] Clinical Trials Center, Yonsei University Health System, Seoul, Korea | [q] Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea

Correspondence: [*] Correspondence to: Sang Won Seo, MD, Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: +82 2 3410 1233; Fax: +82 2 3410 0052; E-mail: sangwonseo@empal.com.

Abstract: 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.

Keywords: Alzheimer's disease, amyloid burden, apolipoprotein E4, cerebrovascular disease

DOI: 10.3233/JAD-130461

Journal: Journal of Alzheimer's Disease, vol. 40, no. 4, pp. 877-886, 2014