Detection of the described mutation in the promoter region of APP can be used in to diagnose familial Alzheimer's disease. In addition, it provides a novel method for the construction of transgenic cell lines or model organisms with increased APP production which can model Alzheimer´s disease.
Summary of the invention
Alzheimer´s disease (AD) can be caused by mutations in the amyloid precursor protein (APP) or the presenilins which frequently increase the production of amyloid-β42 peptide, thereby fostering its deposition in plaques.
Overproduction of APP due to a duplication of the APP-gene or due to mutations in the regulatory sequences in the APP promoter was shown to lead to AD via increased production of Aβ.
Several point mutations in the proximal promoter region of the APP were identified only in AD patients (-118C>A, -369C>G, -479C>T, -534G>A). These mutations result in increased expression of APP due to differential affinity of nuclear factors for these mutated sites.