Generation of a humanized Abeta expressing mouse demonstrating aspects of Alzheimer's disease-like pathology

We generated knock-in mice that express wildtype human Abeta under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Abeta sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. knock-in mouse model that expresses human non-mutated Abeta in the natural context of the endogenous mouse APP gene