INSOLUBLE aggregates of the amyloid p-peptide (AP) is a major constituent of senile plaques found in brains of Alzheimer disease (AD) patients. The detrimental effects of aggregated A beta is associated with an increased intracellular Ca2+ concentration ([Ca2+](i)). We examined the effects of AP(25-35) on [Ca2+](i) and intracellular H+ concentration ([H+](i)) in single hippocampal neurons by real time fluorescence imaging using the Ca2+- and H+-specific ratio dyes, indo-1 and SNARF-1. Incubation of these cultures with AP(25-35) for 3-12 days in vitro increased [Ca2+](i) and [H+](i) in large, NMDA-responsive neurons. (C) 1998 Rapid Science Ltd.