NEURONAL NITRIC-OXIDE SYNTHASE (NNOS) MESSENGER-RNA EXPRESSION AND NADPH-DIAPHORASE STAINING IN THE FRONTAL-CORTEX, VISUAL-CORTEX AND HIPPOCAMPUS OF CONTROL AND ALZHEIMERS-DISEASE BRAINS

Neuronal nitric oxide synthase (nNOS) mRNA levels and NADPH diaphorase (NADPH-d) staining were compared in the frontal cortex, visual cortex and hippocampus (dentate gyrus and CA subfields of Ammon's horn) of f ive Alzheimer's disease (AD) and six control brains. The cellular abun dance of nNOS mRNA was quantified by in-situ hybridisation using S-35- labelled antisense oligonucleotides complementary to the human nNOS se quence. Although the mean level of nNOS expression was decreased in al l three regions in AD cases as compared to controls, it did not reach significance. Neurones positively labelled for nNOS mRNA and neurones positive for NADPH-d histochemistry displayed similar distributions in control and AD cases. In AD brains the density of neurones having det ectable levels of nNOS mRNA was significantly decreased in the white m atter underlying the frontal cortex (P < 0.05) but not in the frontal cortex gray matter; no change was observed in the gray or white matter of the visual cortex in AD, The number of cells expressing detectable levels of nNOS mRNA in the hippocampus was also significantly decreas ed (P < 0.05) in AD. The density of NADPH-d-positive cells was not sig nificantly decreased in the gray or white matter of the frontal or vis ual cortices in AD compared to controls; however, the number of NADPH- d-positive cells was significantly decreased in the hippocampus (P < 0 .01). These data indicate that although the cellular abundance of nNOS mRNA is not significantly decreased in these three regions in AD, the re is a significant decrease in the number of cells expressing detecta ble levels of nNOS mRNA in the white matter underlying the frontal cor tex and in the dentate gyrus and CA subfields of the hippocampus in AD . Futhermore, there was also a significant decrease in the number of N ADPH-d-positive cells in the dentate gyrus and CA subfields of the hip pocampus in AD as compared to controls. These results suggest specific populations of nNOS/NADPH-d cells in the white matter underlying the frontal cortex and in the hippocampus are vulnerable in AD. The implic ations of these findings are discussed.