Do Copy Number Changes in CACNA2D2, CACNA2D3, and CACNA1D Constitute a Predisposing Risk Factor for Alzheimer's Disease?

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.