The significance of the Swedish APP670/671 mutation for the development of Alzheimer's disease amyloidosis.

Alzheimer's disease is characterized histopathologically by the detection of amyloid plaques and tangles in the brains of its victims. A major component of the amyloid plaques, the beta-amyloid peptide, is a metabolite of a larger transmembrane protein termed the amyloid precursor protein (APP). Several pathogenic mutations causing Alzheimer's disease have been identified in the APP gene, situated on chromosome 21. One of these is a double missense mutation in exon 16 of the APP gene which occurs in a large Swedish pedigree. Studies with transfected cell cultures have shown that cells expressing this double mutation release approximately 7 times more beta-amyloid than their wild type counterparts. Possible mechanisms whereby the APP mutations cause Alzheimer's disease are considered here against the background of current understanding of the physiological role and processing of APP.