In 15 months old 3xTg-AD mice, once amyloid plaques and hyperphosphorylated tau are abundant, the dendritic spine density was significantly reduced not only around amyloid plaques (d<50 μm) (Fig. 1A, 1C, and 1D; hippocampus: 0.80±0.02 μm−1 vs. 1.01±0.03 μm−1, P<0.001; frontal cortex: 0.46±0.01 μm−1 vs. 0.54±0.02 μm−1, p<0.001) but also in areas distant to plaques (d>50 μm) compared to controls (Fig. 1B, 1C, and 1D; hippocampus: 0.89±0.02 μm−1 vs. 1.01±0.03 μm−1, p<0.01; frontal cortex: 0.51±0.01 μm−1 vs. 0.54±0.02 μm−1, P<0.05). This evidence concerns the gene MAPT and Alzheimer disease.