Differential display reveals deteriorated mRNA levels of NADH3 (complex I)in cerebellum of patients with Down Syndrome

Although gene hunting has been carried out in Down Syndrome (DS) cells, inf ormation on expressional differences in DS brain is limited. We have recent ly described expressional differences in fetal DS brain but cannot assign t hese findings to "DS per" se or simply to "neurodegeneration". We therefore performed gene hunting in cerebellum of adult patients with DS and Alzheimer's disease (AD) neuropathology, AD and controls. The gene hunting method used was differential display and pools of the indi vidual groups were examined to rule out allelic differences. Differential display revealed the absence of a band, identified by sequenci ng and gene bank work as matching the NADH3 gene (99.1% identity) in cerebe llum of DS patients. Dot blots showed the presence of NADH3 signals in only two out of 7 DS patients. We show at the transcriptional level that a mitochondrial enzyme, the compl ex I, NADH3, is significantly downregulated in DS cerebellum. This extends previous work on deficiencies of the electron transport chain in platelets of patients with DS.