Down’s syndrome and Alzheimer’s disease: two sides of the same coin

Abstract

All Down’s syndrome individuals develop Alzheimer’s disease (AD) neuropathology by the age of 40 years. To unite the two diseases under one hypothesis, we have suggested that classical AD, both of the genetic and late-onset sporadic forms, might be promoted by small numbers of trisomy 21 cells developing during the life of the affected individual. Recent evidence from several laboratories will be presented, which strongly supports the trisomy 21 hypothesis that defects in mitosis, and particularly in chromosome segregation, may be a part of the AD process. Specifically, genetic mutations that cause familial AD disrupt the cell cycle and lead to chromosome aneuploidy, including trisomy 21, in transgenic mice and transfected cells; cells from both familial and sporadic AD patients exhibit chromosome aneuploidy, including trisomy 21. The possibility that many cases of AD are mosaic for trisomy 21 suggests novel approaches to diagnosis and therapy.