Most importantly from an AD modeling perspective, our results make it very unlikely that the profound deficits in learning and memory, behavioral abnormalities, neural network dysfunction, and related molecular alterations in hippocampal neurons of hAPP-J20 mice are caused by reduced Zbtb20 levels rather than by the expression of FAD-mutant hAPP, providing novel mechanistic insights into the pathogenesis of this model’s phenotype. The gene discussed is ZBTB20; the disease is Alzheimer disease.