Do copy number changes in CACNA2D2, CACNA2D3, and CACNA1D constitute a predisposing risk factor for Alzheimer's disease

Abstract

Dysregulation of calcium (Ca2+) 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 Ca2+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 Ca2+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 Ca2+channels; these duplications of voltage-gated Ca2+channel genes is consistent with the critical role of calcium signaling in molecular processes underlying memory as has been demonstrated by several studies.