According to the schematic figure (Figure 1), we proposed that the activation of TRPM2 channels in microglia and astrocytes produces Ca2+ overload and subsequent inflammation and oxidative stress which results in mitochondrial dysfunctions, [Ca2+]i increase, Aβ accumulation in neurons, PSD95 reduction, glutamate receptor dysfunction, and finally change of plasticity and dementia. This evidence concerns the gene DLG4 and dementia.