Associations between APOE genotype and cerebral small-vessel disease: a longitudinal study
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Xiao Luo1,*, Yerfan Jiaerken1,*, Xinfeng Yu1, Peiyu Huang1, Tiantian Qiu1, Yunlu Jia3, Kaicheng Li1, Xiaojun Xu1, Zhujing Shen1, Xiaojun Guan1, Jiong Zhou2 and Minming Zhang1, for The Alzheimer’s Disease Neuroimaging Initiative (ADNI)
1Department of Radiology, The Second Affiliated Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
2Department of Neurology, The Second Affiliated Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
3Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
*These authors have contributed equally to this work
Minming Zhang, email: [email protected]
Keywords: apolipoprotein E (APOE), cerebral small-vascular disease (CSVD), white matter hyperintensities (WMH), dilated perivascular space (dPVS), cognition
Abbreviations: APOE: apolipoprotein E; CSVD: cerebral small-vascular disease; WMH: white matter hyperintensities; dPVS: dilated perivascular space; MBs: microbleeds
Received: December 29, 2016 Accepted: April 07, 2017 Published: May 09, 2017
Objective: It remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data.
Method: There were 135 healthy elderly (including ε2, ε4 allele carriers and ε3 homozygotes) who had completed two years’ follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimer’s disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD.
Results: We found that APOE ε4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE ε4 carriers had significantly decreased Aβ1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and ε4 allele was related with declining trend of cognition.
Conclusion: Our findings suggested APOE ε4 allele was associated with increased Aβ deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and ε4 allele can exert long-term detrimental effects on individual’s trajectory of cognition.
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