REGIONAL AND CELLULAR-LOCALIZATION OF PRESENILIN-2 RNA IN RAT AND HUMAN BRAIN

In situ hybridization probes selective for presenilin-2 (PS-2) were us ed to determine the regional and cellular expression pattern of PS-2 m RNA in rat and human brain. In rat brain, the greatest expression of P S-2 mRNA is in the granule cell layers of the dentate gyrus and cerebe llum. Molecular layers within these structures are virtually devoid of signal. Cortical expression of PS-2 message is restricted to neuronal layers, while the hybridization signal is weak or absent in molecular layers and white matter. Kidney, liver, and spleen display moderate l evels of PS-2 message. A PS-2 sense strand probe produced no specific signals in any tissue. In human brain, the greatest hybridization sign al for PS-2 is present in the granule bells of the cerebellum. Within hippocampus, the granule cell layer of dentate is strongly labeled, wi th CA3 pyramidal neurons also clearly visible. A laminar expression pa ttern is seen in the neuronal layers of human frontal and temporal cor tex, with the deeper laminae having the strongest signals. These data are consistent with a primarily neuronal localization of PS-2 mRNA wit hin the brains of both rat and human. Within the limitations of the an alysis, it appears that virtually every neuron is labeled, and differe nces in the intensity of labeling are associated with both neuron size /density and brain region. The distribution of PS-2 RNA is not restric ted to those regions having the greatest pathology in Alzheimer's dise ase. However, one unusual pathological feature of PS-2 mutations causi ng AD is the presence of cerebellar amyloid plaques in some cases. It is intriguing, in this context, that PS-2 RNA is enriched in the cereb ellum, especially in human specimens. (C) 1997 Academic Press.