Free intracellular calcium in peripheral cells in Alzheimer's disease.

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.