title: Calcium in Alzheimer's disease pathogenesis: too much, too little or in the wrong place?
abstract: Our understanding of the molecular genetics and biochemical pathology of Alzheimer's disease has progressed tremendously in the past decade. The metabolism of amyloid beta-peptide is being unraveled, and specific anti-amyloid therapies are now in clinical trials worldwide. The precise biophysical structure of the amyloid beta-peptide that causes neuronal dysfunction remains under investigation, as does the interaction between amyloid peptides and tau hyperphosphorylation, but these two molecules likely play key roles in neuronal dysfunction in Alzheimer's disease. Despite these advances, the cell biology of neuronal dysfunction and cell death in the Alzheimer's disease brain remains poorly understood. This brief review will explore the role of calcium (Ca2+) in neuronal death occurring during Alzheimer's disease. The evidence for glutamate receptor-mediated Ca;2+ overload, or excitotoxicity, and other derangements of Ca2+ homeostasis in cell culture and animal models of Alzheimer's disease is reviewed. Finally, we raise the possibility that some of the neuronal death observed in Alzheimer's disease might be associated with a reduction in rather than an increase in cytosolic Ca2+ levels, an idea with potentially important therapeutic implications.
authors.affiliation: Department of Biology and Environmental Sciences, University of Sannio, Benevento, Italy. canzoniero@unisannio.it
authors.forename: Lorella M T
authors.initials: LM
authors.lastname: Canzoniero
authors.forename: B Joy
authors.initials: BJ
authors.lastname: Snider
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000502:physiology; D009498:Neurotoxins / Q000378:metabolism; D017470:Receptors, Glutamate / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D017470:Receptors, Glutamate; D002118:Calcium