ALTERATIONS OF INTRACELLULAR CALCIUM REGULATION DURING AGING AND ALZHEIMERS-DISEASE IN NONNEURONAL CELLS

Because of its function as an intracellular messenger in many cells, c alcium plays an important role in signal transduction. Changes in intr acellular free calcium concentration occur in central neurons during a ging and Alzheimer's disease (AD). It is possible that similar changes in peripheral cells could mirror or, at least parallel, similar abnor malities in the brain. Assuming that manifestations of the aging proce ss and AD are also present outside the central nervous system, nonneur onal tissues like lymphocytes could be used to search directly for abn ormalities in cellular calcium regulation in man. Consistent with obse rvations of reduced depolarization-induced Ca2+ rises in dissociated n eurons of aged mice, corresponding age-related changes of reduced mito gen-induced Ca2+ responses were observed both in mouse lymphocytes and , more importantly, in circulating human lymphocytes. With respect to AD, Ca2+ responses after stimulation were unaltered (compared to norma l controls). In addition, freshly prepared human lymphocytes showed el evated mitogen-induced Ca2+ responses after exposure to beta-amyloid, the main component of senile plaques in AD. These findings again paral lel our observations that this peptide amplifies the K+-induced Ca2+ r ise in acutely dissociated mouse brain cells. Thus, the lymphocyte see ms to be a valuable model to study the effects of beta-amyloid in man. In a preliminarey study with AD-patients, sensitivity of the lymphocy tes to beta-amyloid's effects on Ca2+ rise was reduced, an observation which was entirely unexpected. Nevertheless, such studies indicate ly mphocytes may represent a promising candidate for a peripheral marker of AD and can contribute to the understanding of the disease process.