Eckert A, Förstl H, Zerfass R, Hennerici M, Müller W E
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany.
Neurobiol Aging. 1997 May-Jun;18(3):281-4. doi: 10.1016/s0197-4580(97)80308-9.
The goal of the present study was to evaluate several parameters of free intracellular Ca2+ regulation ([Ca2+]i) in Alzheimer's disease (AD) in a very large group of patients (n = 50) and nondemented controls (n = 41), using blood lymphocytes and neutrophils as two different peripheral model systems. We found no major difference, because neither the basal [Ca2+]i, nor the activation-induced Ca2+ responses differed among neutrophils or lymphocytes from aged controls and AD patients. However, we observed a delayed Ca2+ response of AD lymphocytes after phytohemagglutinin (PHA) stimulation, indicating an impaired function of Ca2+ influx-controlling mechanisms, because Ca2+ release from intracellular stores appears to be unchanged. Because the PHA-induced Ca2+ response in lymphocytes is accelerated by beta-amyloid (Beta A) similarly to its effects on central neurons, we also investigated the effect of beta A on Ca2+ signalling with regard to AD-related alterations. In contrast to lymphocytes from aged controls, the amplifying effect on Ca2+ signalling was significantly reduced in lymphocytes from a high percentage of AD patients. The results are discussed with respect to their diagnostic potential and to a possible involvement of altered beta A sensitivity of lymphocytes in the pathophysiology of AD.
本研究的目的是，以血液淋巴细胞和中性粒细胞作为两种不同的外周模型系统，在一大组患者（n = 50）和非痴呆对照者（n = 41）中评估阿尔茨海默病（AD）患者细胞内游离钙离子调节（[Ca2+]i）的几个参数。我们未发现显著差异，因为老年对照者和AD患者的中性粒细胞或淋巴细胞中，基础[Ca2+]i以及激活诱导的钙离子反应均无差异。然而，我们观察到植物血凝素（PHA）刺激后AD淋巴细胞的钙离子反应延迟，这表明钙离子内流控制机制功能受损，因为细胞内钙库的钙离子释放似乎未改变。由于淋巴细胞中PHA诱导的钙离子反应与β-淀粉样蛋白（βA）对中枢神经元的作用类似，也会被其加速，因此我们还研究了βA对钙离子信号传导的影响以及与AD相关的改变。与老年对照者的淋巴细胞不同，高比例AD患者的淋巴细胞中，βA对钙离子信号传导的放大作用显著降低。我们将结合这些结果的诊断潜力以及淋巴细胞βA敏感性改变可能参与AD病理生理学过程这一情况进行讨论。
