A modified amyloid precursor protein can be expressed from a DNA construct comprising an APP DNA sequence, or a fragment or artificial substrate thereof, encoding the mutation I45W, I45Y V46W or V46Y (numbering relative to A4CT); the use of the DNA construct in the generation of cell lines or transgenic animals and the use of these proteins or such transgenic animals in the diagnosis of Alzheimer's Disease and screening putative drugs against Alzheimer's Disease are also described.