title: Do Copy Number Changes in CACNA2D2, CACNA2D3, and CACNA1D Constitute a Predisposing Risk Factor for Alzheimer's Disease?
abstract: Dysregulation of calcium (Ca(2+)) homeostasis is now being recognized to be a key step in the pathogenesis of Alzheimer's disease (AD). Data from the literature, in particular the association between AD and polymorphism that interfere with Ca(2+) homeostasis indicates the presence of genetic factors in this process; further, presenilins mutations, which are known to cause the familial form of AD, are involved in the regulation of intracellular Ca(2+) stores. Here, we wish to draw attention to rare DNA copy number variations identified in two subjects with late-onset AD that led to partial or full duplication of genes that encode different subunits of the same type of voltage-gated Ca(2+) channels; these duplications of voltage-gated Ca(2+) channel genes is consistent with the critical role of calcium signaling in molecular processes underlying memory as has been demonstrated by several studies.
authors.affiliation: Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo Brazil.
authors.forename: Darine
authors.initials: D
authors.lastname: Villela
authors.affiliation: Discipline of Geriatrics, Department of Clinical Medicine, School of Medicine, University of São Paulo, São PauloBrazil; Brazilian Aging Brain Study Group - LIM22, Department of Pathology, School of Medicine, University of São Paulo, São PauloBrazil.
authors.forename: Claudia K
authors.initials: CK
authors.lastname: Suemoto
authors.affiliation: Brazilian Aging Brain Study Group - LIM22, Department of Pathology, School of Medicine, University of São Paulo, São PauloBrazil; Department of Pathology, School of Medicine, University of São Paulo, São PauloBrazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pasqualucci
authors.affiliation: Brazilian Aging Brain Study Group - LIM22, Department of Pathology, School of Medicine, University of São Paulo, São PauloBrazil; Memory and Aging Center, Department of Neurology, University of California, San Francisco, San Francisco, CAUSA.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: Human Genome and Stem-Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
keywords: Alzheimer’s disease; CNVs; Ca2+; array-CGH; copy number variations