The two critical forms of dementia are Alzheimer's disease (AD) and vascular dementia (VD). The alterations of Ca²⁺/calmodulin/CaMKII/Ca_V1.2 signaling in AD and VD have not been well elucidated. Here we have demonstrated changes in the levels of Ca_V1.2, calmodulin, p-CaMKII, p-CREB and BDNF proteins by Western blot analysis and the co-localization of p-CaMKII/Ca_V1.2 by double-labeling immunofluorescence in the hippocampus of APP/PS1 mice and VD gerbils. Additionally, expression of these proteins and intracellular calcium levels were examined in cultured neurons treated with Aβ_1–42. The expression of Ca_V1.2 protein was increased in VD gerbils and in cultured neurons but decreased in APP/PS1 mice; the expression of calmodulin protein was increased in APP/PS1 mice and VD gerbils; levels of p-CaMKII, p-CREB and BDNF proteins were decreased in AD and VD models. The number of neurons in which p-CaMKII and Ca_V1.2 were co-localized, was decreased in the CA1 and CA3 regions in two models. Intracellular calcium was increased in the cultured neurons treated with Aβ_1–42. Collectively, our results suggest that the alterations in Ca_V1.2, calmodulin, p-CaMKII, p-CREB and BDNF can be reflective of an involvement in the impairment in memory and cognition in AD and VD models.