Eckert A, Förstl H, Zerfass R, Oster M, Hennerici M, Müller W E
Department of Psychopharmacology, Klinikum Mannheim, University of Heidelberg, Federal Republic of Germany.
J Neural Transm Suppl. 1998;54:201-10. doi: 10.1007/978-3-7091-7508-8_20.
Free intracellular calcium ([Ca2+]i) represents probably the most important intracellular messenger for many signal transduction pathways. Due to this crucial role of [Ca2+]i, it has been assumed that alterations of [Ca2+]i are critically involved in brain aging and in the pathophysiology of Alzheimer's disease (AD). This hypothesis is corroborated by several studies demonstrating changes of [Ca2+]i in peripheral cells from AD patients. However, the findings are still controversial. Using blood lymphocytes and neutrophils as two different peripheral model systems, we evaluated several parameters of intracellular Ca2+ regulation in a very large group of AD patients and non-demented controls. We found no major difference in Ca2+ homeostasis, since 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. Furthermore, we studied whether differences exist in Ca2+ regulation between lymphocytes from patients with vascular dementia and AD patients, to define AD-specific alterations and to distinguish between the two dementia groups and non-demented control subjects respectively. First evidences indicate that Ca2+ mobilization in lymphocytes is specifically impaired in lymphocytes from patients with vascular dementia.
游离细胞内钙（[Ca2+]i）可能是许多信号转导途径中最重要的细胞内信使。由于[Ca2+]i的这一关键作用，人们认为[Ca2+]i的改变与大脑衰老及阿尔茨海默病（AD）的病理生理学密切相关。多项研究证实AD患者外周细胞中[Ca2+]i发生变化，从而支持了这一假说。然而，这些发现仍存在争议。我们使用血淋巴细胞和中性粒细胞作为两种不同的外周模型系统，对一大群AD患者和非痴呆对照者的细胞内Ca2+调节的几个参数进行了评估。我们发现Ca2+稳态没有重大差异，因为老年对照者和AD患者的中性粒细胞或淋巴细胞的基础[Ca2+]i以及激活诱导的Ca2+反应均无差异。然而，我们观察到在植物血凝素（PHA）刺激后，AD淋巴细胞的Ca2+反应延迟，这表明Ca2+内流控制机制功能受损。此外，我们研究了血管性痴呆患者与AD患者淋巴细胞之间的Ca2+调节是否存在差异，以确定AD特异性改变，并分别区分这两种痴呆组与非痴呆对照者。初步证据表明，血管性痴呆患者淋巴细胞中的Ca2+动员存在特异性受损。
