Intracellular calcium signalling in Alzheimer's disease

Introduction Dysregulation of Ca2+ homeostasis in AD A beta accumulation causes Ca2+ dyshomeostasis Ca2+ dyshomeostasis increases A beta production Presenilins and Ca2+ homeostasis Dysregulation of Ca2+ homeostasis in vivo AD-mediated hyperactivity and synaptic network dysfunction Neuronal hyperactivity: implications for humans Plaque vicinity Conclusions More than two decades ago, dysregulation of the intracellular Ca2+ homeostasis was suggested to underlie the development of Alzheimer's disease (AD). This hypothesis was tested in numerous in vitro studies, which revealed multiple Ca2+ signalling pathways able to contribute to AD pathology. It remained, however, unclear whether these pathways are also activated in vivo, in cells involved in signal processing in the living brain. Here we review recent data analysing intracellular Ca2+ signalling in vivo in the context of previous in vitro findings. We particularly focus on the processes taking place in the immediate vicinity of amyloid plaques and on their possible role for AD-mediated brain dysfunction.