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阿尔茨海默型老年痴呆患者脑脊液中的胆碱酯酶活性

Cholinesterase activities in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

作者信息

Appleyard M E, Smith A D, Berman P, Wilcock G K, Esiri M M, Neary D, Bowen D M

机构信息

University Department of Pharmacology, Oxford.

出版信息

Brain. 1987 Oct;110 ( Pt 5):1309-22. doi: 10.1093/brain/110.5.1309.

Abstract

Acetylcholinesterase (AChE) and nonspecific cholinesterase (nsChE) activities of lumbar ceresbrospinal fluid (CSF) from patients with a clinical or histological diagnosis of Alzheimer's disease have been compared with those of normal age-matched control patients and patients with dementia of non-Alzheimer aetiology. No significant differences in the AChE activity of lumbar CSF from histologically and clinically diagnosed Alzheimer's disease patients and normal age-matched controls were found, although they could be distinguished from controls and other dements by their lower lumbar CSF levels of nsChE activity and by their elevated ratio of AChE/nsChE. A lower level of AChE activity was observed in the lumbar CSF of patients with dementia of non-Alzheimer aetiology. The AChE and nsChE activities of ventricular CSF obtained at postmortem have also been examined. The AChE activity of the ventricular CSF of patients with histologically confirmed Alzheimer's disease was 66% lower than that of age-matched controls; these patients could also be distinguished from normals by their lower levels of nsChE and by the elevated ratio of AChE/nsChE activities. A molecular defect in the AChE in the ventricular CSF of Alzheimer patients is indicated by the finding that the enzyme failed to show inhibition by high concentrations of substrate. The lower level of AChE in ventricular CSF may reflect the changes in this enzyme in forebrain regions of Alzheimer patients. Although it is at present not possible to correlate the lower levels of nsChE found in CSF with any known brain pathology, the significantly altered ratio of AChE/nsChE activities in lumbar CSF may possibly form the basis for a diagnostic test of Alzheimer type dementia.

摘要

已将临床诊断或组织学诊断为阿尔茨海默病患者的腰椎脑脊液(CSF)中的乙酰胆碱酯酶(AChE)和非特异性胆碱酯酶(nsChE)活性,与年龄匹配的正常对照患者以及非阿尔茨海默病因痴呆患者的相应活性进行了比较。在组织学和临床诊断为阿尔茨海默病的患者与年龄匹配的正常对照者的腰椎CSF中,未发现AChE活性有显著差异,尽管通过其较低的腰椎CSF中nsChE活性水平以及升高的AChE/nsChE比值,可将他们与对照者及其他痴呆患者区分开来。在非阿尔茨海默病因痴呆患者的腰椎CSF中观察到较低水平的AChE活性。还检查了死后获得的脑室CSF中的AChE和nsChE活性。组织学确诊为阿尔茨海默病的患者脑室CSF中的AChE活性比年龄匹配的对照者低66%;这些患者也可通过其较低的nsChE水平以及升高的AChE/nsChE活性比值与正常人区分开来。在阿尔茨海默病患者脑室CSF中发现该酶未能显示出高浓度底物的抑制作用,这表明该患者脑室CSF中的AChE存在分子缺陷。脑室CSF中较低水平的AChE可能反映了阿尔茨海默病患者前脑区域中该酶的变化。尽管目前尚无法将CSF中发现的较低水平的nsChE与任何已知的脑病理学联系起来,但腰椎CSF中显著改变的AChE/nsChE活性比值可能构成阿尔茨海默型痴呆诊断试验的基础。

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