Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients
Different Cholinesterase Inhibitor Effects on CSF Cholinesterases in Alzheimer Patients
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DOI：
10.2174/156720509787313961
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发表时间：
2009-02-01
影响因子：
2.1
通讯作者：
Lane, Roger
中科院分区：
文献类型：
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作者：
Nordberg, Agneta;Darreh-Shori, Taher;Lane, Roger
背景资料：本研究旨在比较不同胆碱酯酶抑制剂对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）活性和蛋白水平的影响，在脑脊液（CSF）的阿尔茨海默病（AD）patients.Methods和Findings：AD患者年龄在50-85岁，随机开放标签治疗口服卡巴拉汀，多奈哌齐或加兰他敏13周。采用Ellman比色法测定乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）活性。通过酶联免疫吸附试验（ELISA）评估蛋白水平。主要分析基于完成者人群（完成第13周评估的随机化患者）。63例患者随机接受治疗。卡巴拉汀导致AChE活性降低42.6%，AChE蛋白水平降低9.3%，BuChE活性降低45.6%，BuChE蛋白水平降低21.8%。加兰他敏使AChE活性降低2.1%，BuChE活性降低0.5%，但使AChE蛋白水平升高51.2%，BuChE蛋白水平升高10.5%。多奈哌齐使AChE和BuChE活性分别增加11.8%和2.8%。多奈哌齐引起AChE增加215.2%，BuChE蛋白水平增加0.4%。平均乙酰胆碱酯酶-通读/突触比率的变化，这可能反映了潜在的神经退行性过程，分别为1.4，0.6和0.4 rivastigmine，多奈哌齐和加兰他敏，foreign.Conclusion：研究结果表明，药理学诱导的差异rivastigmine，多奈哌齐和加兰他敏。卡巴拉汀可持续抑制AChE和BuChE，而多奈哌齐和加兰他敏不抑制BuChE，并与CSF AChE蛋白水平升高相关。临床意义需要评估。
Background: The current study aimed to compare the effects of different cholinesterase inhibitors on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities and protein levels, in the cerebrospinal fluid (CSF) of Alzheimer disease (AD) patients.Methods and Findings: AD patients aged 50-85 years were randomized to open-label treatment with oral rivastigmine, donepezil or galantamine for 13 weeks. AChE and BuChE activities were assayed by Ellman's colorimetric method. Protein levels were assessed by enzyme-linked immunosorbent assay (ELISA). Primary analyses were based on the Completer population (randomized patients who completed Week 13 assessments). 63 patients were randomized to treatment. Rivastigmine was associated with decreased AChE activity by 42.6% and decreased AChE protein levels by 9.3%, and decreased BuChE activity by 45.6% and decreased BuChE protein levels by 21.8%. Galantamine decreased AChE activity by 2.1% and BuChE activity by 0.5%, but increased AChE protein levels by 51.2% and BuChE protein levels by 10.5%. Donepezil increased AChE and BuChE activities by 11.8% and 2.8%, respectively. Donepezil caused a 215.2% increase in AChE and 0.4% increase in BuChE protein levels. Changes in mean AChE-Readthrough/Synaptic ratios, which might reflect underlying neurodegenerative processes, were 1.4, 0.6, and 0.4 for rivastigmine, donepezil and galantamine, respectively.Conclusion: The findings suggest pharmacologically-induced differences between rivastigmine, donepezil and galantamine. Rivastigmine provides sustained inhibition of AChE and BuChE, while donepezil and galantamine do not inhibit BuChE and are associated with increases in CSF AChE protein levels. The clinical implications require evaluation.