The present invention provides for a recombinant nucleic acid molecule comprising a humanized mouse .beta.-amyloid precursor protein ("APP") gene comprising K670N, M671L and V717F mutations and uses thereof. The present invention further provides for a recombinant nucleic acid molecule comprising a region of a calcium-calmodulin dependent kinase II.alpha. ("CaMKII.alpha.") promoter operatively linked to a .beta.-amyloid precursor protein ("APP") gene comprising at least one mutation and uses thereof.