NEURONAL AND GLIAL GENE-EXPRESSION IN NEOCORTEX OF DOWNS-SYNDROME ANDALZHEIMERS-DISEASE

The association cortex of Down's syndrome (DS) predictably and prematu rely undergoes neurofibrillary degeneration of Alzheimer type. Hence s tudies of DS are potentially useful in defining the earliest pathogene tic events in Alzheimer's disease (AD). Previous reports have describe d altered expression of several mRNAs in AD cortex; but the pathogenet ic stage at which expression of these mRNAs begins to deviate from the norm has not been defined. We have examined this issue in neocortex o f DS. Expression of mRNAs, known to be altered in AD cortex, was studi ed by Northern analysis, comparing frontal cortex of DS (15-45 years) with age-matched controls and with AD. Chromosome 21- and non-21-encod ed mRNAs were studied, including transcripts expressed preferentially in neurons (neurofilament light subunit and amyloid precursor transcri pts) and in glia (glial fibrillary acidic protein [GFAP] and S100beta) . Chromosome 21-encoded mRNAs were increased in DS cortex as expected. Except in the DS case with extensive neurofibrillary degeneration, GF AP was expressed at levels significantly below the control, suggesting that trisomy 21 exerts a suppressive effect on GFAP gene expression. We found no instance in which AD-type changes of transcript expression preceded the appearance of neurofibrillary degeneration. The findings indicate that in trisomy 21, certain changes of mRNA prevalence previ ously described for AD neocortex are not a necessary antecedent to neu rofibrillary degeneration.