Yi Dahyun, Lee Dong Y, Sohn Bo K, Choe Young M, Seo Eun H, Byun Min S, Woo Jong I
Department of Neuropsychiatry and Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Department of Neuropsychiatry and Clinical Research Institute, Seoul National University Hospital, Seoul, South Korea.
Am J Geriatr Psychiatry. 2014 Oct;22(10):961-70. doi: 10.1016/j.jagp.2013.12.173. Epub 2014 Jan 4.
Although apolipoprotein (APOE) ε4 allele is a well-established risk factor for late-onset Alzheimer disease (AD), the mechanism of its effects on AD pathogenesis is not fully understood. We aimed to investigate the effects of APOE genotype on regional cerebral glucose metabolism in cognitively normal (CN) elderly. We further tried to elucidate whether or not such effects are associated with beta-amyloid protein (Aβ) deposition.
31 CN elderly participants underwent clinical examination, a range of neuropsychological tests, APOE genotyping, and Pittsburgh compound-B- and fluorodeoxyglucose-PET scans.
17 APOE ε4 carriers and 15 non-carriers were included. Both hypometabolic and hypermetabolic regions were observed in ε4 carriers compared with noncarriers when age, education, and sex were controlled. When the degree of global cerebral Aβ deposition was adjusted, the hypometabolic regions in the temporo-parietal area (i.e., BA 22 and 39) largely disappeared, whereas the hypermetabolic regions persisted in medial frontal and anterior temporal areas (i.e., BA 38, 11, and 39). Behaviorally, verbal episodic memory scores of APOE ε4 carriers were slightly lower than those of noncarriers, though still within normal range.
Our findings indicate that decreased cerebral glucose metabolism in the temporoparietal junction associated with APOE ε4 in CN elderly appears to be mediated by Aβ deposition, and the effect of APOE ε4 on hypermetabolism in the frontal and anterior temporal regions is independent of Aβ and may be associated with presence of compensatory mechanism in CN elderly with the ε4 allele.
尽管载脂蛋白（APOE）ε4等位基因是晚发性阿尔茨海默病（AD）公认的危险因素，但其对AD发病机制的影响尚不完全清楚。我们旨在研究APOE基因型对认知正常（CN）老年人脑区葡萄糖代谢的影响。我们还试图阐明这种影响是否与β-淀粉样蛋白（Aβ）沉积有关。
31名CN老年参与者接受了临床检查、一系列神经心理学测试、APOE基因分型以及匹兹堡化合物B和氟脱氧葡萄糖PET扫描。
纳入了17名APOE ε4携带者和15名非携带者。在控制年龄、教育程度和性别后，与非携带者相比，ε4携带者中观察到了代谢减低和代谢增高区域。当调整全脑Aβ沉积程度时，颞顶叶区域（即BA 22和39）的代谢减低区域基本消失，而额叶内侧和颞叶前部区域（即BA 38、11和39）的代谢增高区域持续存在。在行为方面，APOE ε4携带者的言语情景记忆得分略低于非携带者，尽管仍在正常范围内。
我们的研究结果表明，CN老年人中与APOE ε4相关的颞顶叶交界处脑葡萄糖代谢降低似乎由Aβ沉积介导，APOE ε4对额叶和颞叶前部区域代谢增高的影响独立于Aβ，可能与携带ε4等位基因的CN老年人存在代偿机制有关。
