载脂蛋白E对有明显记忆问题的老年人阿尔茨海默病生物标志物的影响。
APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern.
作者信息
Risacher Shannon L, Kim Sungeun, Nho Kwangsik, Foroud Tatiana, Shen Li, Petersen Ronald C, Jack Clifford R, Beckett Laurel A, Aisen Paul S, Koeppe Robert A, Jagust William J, Shaw Leslie M, Trojanowski John Q, Weiner Michael W, Saykin Andrew J
机构信息
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
出版信息
Alzheimers Dement. 2015 Dec;11(12):1417-1429. doi: 10.1016/j.jalz.2015.03.003. Epub 2015 May 7.
INTRODUCTION
This study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC).
METHODS
Cognitively normal, SMC, and early mild cognitive impairment participants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [(18)F]Florbetapir amyloid positivity on CSF biomarkers.
RESULTS
SMC ε4+ showed greater amyloid deposition than SMC ε4-, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+ showed lower amyloid beta 1-42 and higher tau/p-tau than ε4-, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC.
DISCUSSION
SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at-risk nature of the SMC group and the importance of APOE in mediating this risk.
引言
本研究评估了载脂蛋白E（APOE）ε4携带者状态对有显著记忆问题（SMC）的认知正常老年人的阿尔茨海默病影像学和脑脊液（CSF）生物标志物的影响。
方法
来自阿尔茨海默病神经影像学倡议组织的认知正常、有SMC且有早期轻度认知障碍的参与者按APOE ε4携带者状态进行分组。重点针对SMC评估诊断和APOE的影响。在SMC中进行的其他分析评估了APOE与[（18）F]氟代贝他吡淀粉样蛋白阳性之间的相互作用对CSF生物标志物的影响。
结果
SMC ε4+组比SMC ε4-组显示出更大的淀粉样蛋白沉积，但没有代谢减退或内侧颞叶（MTL）萎缩。SMC ε4+组比ε4-组显示出更低的淀粉样蛋白β1-42水平和更高的tau/p-tau水平，这在APOE ε4+且脑淀粉样蛋白阳性的SMC中最为异常。
讨论
SMC APOE ε4+组在淀粉样蛋白和tau生物标志物方面显示出异常变化，但没有代谢减退或MTL神经变性，这反映了SMC组的风险性质以及APOE在介导这种风险中的重要性。
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