title: White matter hyperintensities are associated with amyloid burden in APOE4 non-carriers.
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.
authors.affiliation: Department of Neurology, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Noh
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Korea.
authors.forename: Seun
authors.initials: S
authors.lastname: Jeon
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Korea.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Geon Ha
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hanna
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Neurology, Inha University Hospital, Inha University School of Medicine, Incheon, Korea.
authors.forename: Cindy W
authors.initials: CW
authors.lastname: Yoon
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byoung Seok
authors.initials: BS
authors.lastname: Ye
authors.affiliation: Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Institute for Stroke and Dementia Research, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Ewers
authors.affiliation: University of California, San Francisco, San Francisco, CA, USA Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, SanFrancisco, CA, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Weiner
authors.affiliation: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, Queen Square, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Werring
authors.affiliation: Clinical Trials Center, Yonsei University Health System, Seoul, Korea.
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Kang
authors.affiliation: Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Chang Soo
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D003072:Cognition Disorders / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D015140:Dementia, Vascular / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006801:Humans; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D012044:Regression Analysis; D012189:Retrospective Studies; D013223:Statistics as Topic; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D013844:Thiazoles
keywords: Alzheimer's disease; amyloid burden; apolipoprotein E4; cerebrovascular disease