SOMATOSTATIN MESSENGER RNA-CONTAINING NEURONS IN ALZHEIMERS-DISEASE -AN IN-SITU HYBRIDIZATION STUDY IN HIPPOCAMPUS, PARAHIPPOCAMPAL CORTEXAND FRONTAL-CORTEX

The level of expression of somatostatin messenger RNA-containing neuro ns in human brain was visualized and quantified by in situ hybridizati on with a S-35-labelled oligonucleotide complementary to amino acids 9 6-111 of the preprosomatostatin complementary DNA sequence. The analys is was carried out in the frontal and parahippocampal cortices and hip pocampus of six age- and post mortem delay-matched Alzheimer's disease and control brains. By northern blot analysis, in frontal cortex samp les, 18S rRNA degradation was identical in control and Alzheimer brain s and somatostatin messenger RNAs migrated as a single band of 1 kb. B y in situ hybridization, specificity was demonstrated by abolition of the signal using either an excess of unlabelled antisense probe or usi ng a labelled sense probe. Somatostatin messenger RNA-containing neuro ns displayed a similar regional and subregional distribution in contro l subjects and patients with Alzheimer's disease, being more abundant in the frontal cortex, followed by the hippocampus and the parahippoca mpal cortex. An overall reduction of labelled cell density was observe d in patients with Alzheimer's disease (frontal cortex gray matter: -4 1%; white matter: -66%; hippocampus: -44%; parahippocampal cortex whit e matter: -40%). Due to a great variation between brains, this decreas e only reached significance in the parahippocampal cortex (-59%, P < 0 .05). A significantly lower level of expression of somatostatin messen ger RNA per somatostatinergic cell was observed in the hippocampus of Alzheimer's disease patients (-47%, P < 0.05), but not in frontal cort ex gray (-17%) and white (-36%) matter and parahippocampal cortex gray (-42%) and white (-29%) matter. These data are in accordance with the distribution of somatostatin cells as visualized by immunohistochemis try in human brain. They indicate that the ability of cortical cells t o express somatostatin messenger RNA is partially preserved in Alzheim er disease brains and that the decrease in the amount of somatostatin messenger RNA per cell is restricted to the hippocampal formation.