title: Calcium signalling and Alzheimer's disease.
abstract: New insights into how Ca(2+) regulates learning and memory have begun to provide clues as to how the amyloid-dependent remodelling of neuronal Ca(2+) signalling pathways can disrupt the mechanisms of learning and memory in Alzheimer's disease (AD). The calcium hypothesis of AD proposes that activation of the amyloidogenic pathway remodels the neuronal Ca(2+) signalling pathways responsible for cognition by enhancing the entry of Ca(2+) and/or the release of internal Ca(2+) by ryanodine receptors or InsP(3) receptors. The specific proposal is that Ca(2+) signalling remodelling results in a persistent elevation in the level of Ca(2+) that constantly erases newly acquired memories by enhancing the mechanism of long-term depression (LTD). Neurons can still form memories through the process of LTP, but this stored information is rapidly removed by the persistent activation of LTD. Further dysregulation in Ca(2+) signalling will then go on to induce the neurodegeneration that characterizes the later stages of dementia.
authors.affiliation: The Babraham Institute, Babraham, Cambridge, CB22 3AT, UK. michael.berridge@bbsrc.ac.uk
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Berridge
mesh_terms: D000199:Actins / Q000378:metabolism; D000544:Alzheimer Disease / Q000503:physiopathology*; D000682:Amyloid / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D006801:Humans; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D008568:Memory / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology
chemical_list: D000199:Actins; D000682:Amyloid; D016229:Amyloid beta-Peptides; D018091:Receptors, AMPA; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium