Quantitative synapse analysis revealed a pronounced, 30% reduction in synapses on the apical tuft in juvenile APP/PS1 mice compared to wild-type littermates, a difference that was highly significant (WT 3.91 ± 0.18 vs. AD 2.79 ± 0.15 synaptic puncta/μm, p = 2.6 × 10−5; Figures 3A–3D; also see Figure S3 for animal-averaged puncta densities). This evidence concerns the gene PSEN1 and Alzheimer disease.