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

We generated knock-in mice that express wildtype human Aß under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aß 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. Overall design: knock-in mouse model that expresses human non-mutated Aß in the natural context of the endogenous mouse APP gene