BETA-AMYLOID PROTEIN AMPLIFIES CALCIUM SIGNALING IN CENTRAL NEURONS FROM THE ADULT-MOUSE

The role of β-amyloid in Alzheimer′s disease and its cellular mechanism of action are still unclear. Based on observations that β-amyloid influences neuronal calcium homeostasis we investigated the effect of the peptide on K+-induced enhancement of free intracellular calcium in dissociated neurons from adult mice. Preincubation with β-amyloid fragment 25-35 at concentrations ≥0.05μmol/l resulted in marked amplification of the K+-induced Ca2+ response. This effect was also observed with fragment 1-40, whereas fragment 1-28 or 12-28 did not affect the Ca2+ response. This preparation therefore presents a valuable model to investigate the action of β-amyloid ex vivo in individual animals. Our findings suggest a small but consisting destabilizating effect of β-amyloid on neuronal Ca2+ homeostasis resulting in chronically increased neuronal vulnerability. © 1993 Academic Press. All rights reserved.