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携带载脂蛋白Eε4等位基因的阿尔茨海默病患者脑脊液中丁酰胆碱酯酶水平差异与认知功能及脑葡萄糖代谢的关系

Differential CSF butyrylcholinesterase levels in Alzheimer's disease patients with the ApoE epsilon4 allele, in relation to cognitive function and cerebral glucose metabolism.

作者信息

Darreh-Shori T, Brimijoin S, Kadir A, Almkvist O, Nordberg A

机构信息

Karolinska Institutet, Department of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Stockholm, Sweden.

出版信息

Neurobiol Dis. 2006 Nov;24(2):326-33. doi: 10.1016/j.nbd.2006.07.013. Epub 2006 Sep 14.

Abstract

Butyrylcholinesterase (BuChE) is increased in the cerebral cortex of Alzheimer's disease (AD) patients, particularly those carrying epsilon4 allele of the apolipoprotein E gene (ApoE) and certain BuChE variants that predict increased AD risk and poor response to anticholinesterase therapy. We measured BuChE activity and protein level in CSF of eighty mild AD patients in relation to age, gender, ApoE epsilon4 genotype, cognition and cerebral glucose metabolism (CMRglc). BuChE activity was 23% higher in men than women (p<0.03) and 40-60% higher in ApoE epsilon4 negative patients than in those carrying one or two epsilon4 alleles (p<0.0004). CSF BuChE level correlated with cortical CMRglc. Patients with high to moderate CSF BuChE showed better cognitive function scores than others. We hypothesize that CSF BuChE varies inversely with BuChE in cortical amyloid plaques. Thus, low BuChE in a patient's CSF may predict extensive incorporation in neuritic plaques, increased neurotoxicity and greater central neurodegeneration.

摘要

丁酰胆碱酯酶(BuChE)在阿尔茨海默病(AD)患者的大脑皮质中升高,尤其是那些携带载脂蛋白E基因(ApoE)ε4等位基因以及某些可预测AD风险增加和对抗胆碱酯酶治疗反应不佳的BuChE变体的患者。我们测定了80例轻度AD患者脑脊液中的BuChE活性和蛋白水平,并将其与年龄、性别、ApoE ε4基因型、认知和脑葡萄糖代谢(CMRglc)进行关联分析。男性的BuChE活性比女性高23%(p<0.03),ApoE ε4阴性患者的BuChE活性比携带一个或两个ε4等位基因的患者高40 - 60%(p<0.0004)。脑脊液BuChE水平与皮质CMRglc相关。脑脊液BuChE水平高至中度的患者认知功能评分优于其他患者。我们推测脑脊液中的BuChE与皮质淀粉样斑块中的BuChE呈负相关。因此,患者脑脊液中低水平的BuChE可能预示着其大量整合到神经炎性斑块中,神经毒性增加以及中枢神经变性加剧。

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