title: Calcium dysregulation in Alzheimer's disease: recent advances gained from genetically modified animals.
abstract: Alzheimer's disease is a progressive and irreversible neurodegenerative disorder that leads to cognitive, memory and behavioural impairments. Two decades of research have implicated disturbances of intracellular calcium homeostasis as playing a proximal pathological role in the neurodegeneration associated with Alzheimer's disease. A large preponderance of evidence has been gained from the use of a diverse range of cell lines. Whilst useful in understanding the principal mechanism of neurotoxicity associated with Alzheimer's disease, technical differences, such as cell type or even the form of amyloid-beta used often underlie conflicting results. In this review, we discuss recent contributions that transgenic technology has brought to this field. For example, the triple transgenic mouse model of Alzheimer's disease has implicated intraneuronal accumulation of the amyloid-beta peptide as an initiating factor in synaptic dysfunction and behavioural deficits. Importantly, this synaptic dysfunction occurs prior to cell loss or extracellular amyloid plaque accumulation. The cause of synaptic dysfunction is unknown but it is likely that amyloid-beta and its ability to disrupt intracellular calcium homeostasis plays a key role in this process.
authors.affiliation: Department of Neurobiology and Behavior, University of California, 1109 Gillespie Neuroscience Building, Irvine CA 92697-4545, USA.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Smith
authors.forename: Kim N
authors.initials: KN
authors.lastname: Green
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans
chemical_list: D002118:Calcium