This paper by Angelo Demuro and Ian Parker reports very careful examination of Ca2+ signaling effects by intracellular amyloid-β oligomers. They used a Xenopus
oocyte model system. In previous studies these authors used a similar approach to evaluate Ca2+ influx mediated by extracellular Aβ oligomers, which make Ca2+-permeable pores in the plasma membranes of cells (1). But some evidence suggested that intracellular Aβ may also play an important role in AD pathology (2). In their studies, Demuro and Parker discover that injection of Aβ42 oligomers (but not monomers) results in Ca2+ responses in Xenopus
oocytes. In contrast to extracellular Aβ42 application, these responses were dominated by inositol triphosphate receptor (InsP3R)-mediated Ca2+ release mechanism. The authors suggest that this can be explained by direct stimulation of phospholipase C-mediated InsP3 production by Aβ42 oligomers, but they do not measure InsP3 production in their paper.
It is more likely that these effects are mediated by positive feedback of Ca2+ on the InsP3R (3), such that...