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阿尔茨海默病患者淋巴细胞的端粒功能障碍

Telomere dysfunction of lymphocytes in patients with Alzheimer disease.

作者信息

Zhang Jianmin, Kong Qingli, Zhang Zhenxin, Ge Pingjiang, Ba Denian, He Wei

机构信息

Chinese Academy of Medical Science and School of Basic Medicine, Peking Union Medical College, Beijing, People's Republic of China.

出版信息

Cogn Behav Neurol. 2003 Sep;16(3):170-6. doi: 10.1097/00146965-200309000-00004.

Abstract

OBJECTIVE

The objective of this study was to investigate the telomerase activity of phytohemagglutinin-activated lymphocytes from patients with Alzheimer disease.

BACKGROUND

There is impairment of immune function in patients with Alzheimer disease, and the perturbation of immune system is involved the pathogenesis of Alzheimer disease. However, the mechanism of the impairment is unclear so far.

METHODS

We analyzed telomerase activities of phytohemagglutinin-activated lymphocytes from 187 cases of patients with Alzheimer disease, 53 cases of patients with vascular dementia, and 80 cases of age-matched healthy controls, respectively. Telomerase activity was measured using the telomeric repeat amplification protocol-based telomerase polymerase chain reaction enzyme-linked immunosorbent assay. We also detected the proliferation activity of peripheral blood mononuclear cells from 10 cases of patients with Alzheimer disease or 10 cases of age-matched healthy controls by [3H] thymidine incorporation.

RESULTS

Telomerase activity of phytohemagglutinin-activated lymphocytes in Alzheimer disease patients was significantly elevated compared with healthy controls (P < 0.01) and vascular dementia patients (P < 0.01), respectively. There was significant statistical correlation between the telomerase activities of lymphocytes and the degree of dementia in Alzheimer disease patients. The proliferation activity of peripheral blood mononuclear cells to phytohemagglutinin was significantly decreased in Alzheimer disease patients compared with age-matched healthy controls (P < 0.01).

CONCLUSIONS

Our data suggest that there could be an accelerated telomere dysfunction in lymphocytes of Alzheimer disease patients, which induces the increase of telomerase activity and the decrease of proliferation activity of lymphocytes, and subsequently results in the impairment of immune function in Alzheimer disease patients.

摘要

目的

本研究旨在调查阿尔茨海默病患者经植物血凝素激活的淋巴细胞的端粒酶活性。

背景

阿尔茨海默病患者存在免疫功能损害,免疫系统紊乱参与了阿尔茨海默病的发病机制。然而,目前该损害的机制尚不清楚。

方法

我们分别分析了187例阿尔茨海默病患者、53例血管性痴呆患者和80例年龄匹配的健康对照者经植物血凝素激活的淋巴细胞的端粒酶活性。采用基于端粒重复序列扩增法的端粒酶聚合酶链反应酶联免疫吸附测定法测量端粒酶活性。我们还通过[3H]胸苷掺入法检测了10例阿尔茨海默病患者或10例年龄匹配的健康对照者外周血单个核细胞的增殖活性。

结果

与健康对照者(P < 0.01)和血管性痴呆患者(P < 0.01)相比,阿尔茨海默病患者经植物血凝素激活的淋巴细胞的端粒酶活性显著升高。淋巴细胞的端粒酶活性与阿尔茨海默病患者的痴呆程度之间存在显著的统计学相关性。与年龄匹配的健康对照者相比,阿尔茨海默病患者外周血单个核细胞对植物血凝素的增殖活性显著降低(P < 0.01)。

结论

我们的数据表明,阿尔茨海默病患者的淋巴细胞可能存在端粒功能加速障碍,这导致端粒酶活性增加和淋巴细胞增殖活性降低,进而导致阿尔茨海默病患者免疫功能受损。

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