Changes of intracellular calcium regulation in Alzheimer's disease and vascular dementia

Free intracellular calcium ([Ca2+](i)) represents probably the most importa nt intracellular messenger for many signal transduction pathways. Due to th is 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 A lzheimer's disease (AD). This hypothesis is corroborated by several studies demonstrating changes of [Ca2+](i) in peripheral cells from AD patients. H owever, the findings are still controversial. Using blood lymphocytes and n eutrophils as two different peripheral model systems, we evaluated several parameters of intracellular Ca2+ regulation in a very large group of AD pat ients and non-demented controls. We found no major difference in Ca2+ homeo stasis, since neither the basal [Ca2+](i), nor the activation-induced Ca2responses 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 dif ferences exist in Ca2+ regulation between lymphocytes from patients with va scular dementia and AD patients, to define AD-specific alterations and to d istinguish between the two dementia groups and non-demented control subject s respectively. First evidences indicate that Ca2+ mobilization in lymphocy tes is specifically impaired in lymphocytes from patients with vascular dem entia.