DOWNS-SYNDROME - UP-REGULATION OF BETA-AMYLOID PROTEIN-PRECURSOR AND TAU-MESSENGER-RNAS AND THEIR DEFECTIVE COORDINATION

Almost all patients >40 years of age with Down's syndrome (DS) develop the pathology characteristic of Alzheimer's disease: abundant beta-am yloid plaques and neurofibrillary tangles. We have investigated the ge ne expression of beta-amyloid protein precursor (APP) and tau in DS an d age-matched control brains and found that levels of both mRNAs were significantly elevated in DS. Such up-regulation was not observed in t wo other neuronal proteins. A correlation between total APP and tau mR NA levels was also found in DS brain but distinct from the pattern obs erved in normal brain. Although a proportionality existed between APP- 695 mRNA and three-repeat tau mRNA in DS, the proportionality between APP-751 mRNA and four-repeat tau mRNA, which is normally present, was not observed. Thus, DS brains are primarily characterized by the up-re gulation of tau mRNA as well as APP mRNA and disruption of the coordin ate expression between APP-751 and four-repeat tau.