WIDESPREAD NEURONAL EXPRESSION OF THE PRESENILIN-1 EARLY-ONSET ALZHEIMERS-DISEASE GENE IN THE MURINE BRAIN

Mutations in the presenilin-1 (S182) gene have been genetically linked to early-onset Alzheimer's disease. To clarify the underlying molecul ar mechanism through which presenilin-1 is involved in the pathogenesi s of this neurodegenerative disorder, the regional and cellular transc ription profile of this gene was characterized in primary cells isolat ed from the murine brain by Northern blot hybridization and in tissue sections by in situ hybridization using digoxigenin-labeled riboprobes . Our results indicate that presenilin-1 mRNA transcripts are widely d istributed throughout the adult mouse brain. furthermore, immunohistoc hemical labeling of hybridized sections indicates that expression was predominantly localized to neuronal cells. Neurons in the hippocampus and cerebral cortex, which are severely compromised in Alzheimer's dis ease, showed prominent expression of presenilin-1. In contrast, white matter areas and endothelial cells do not appear to express presenilin -1 to detectable levels, presenilin-1 transcripts, however, are also p resent less frequently in certain nonneuronal cell populations such as ependymal cells in the choroid plexus. Analysis of primary cells isol ated from murine brain supported the results obtained by in situ hybri dization and showed that cultured primary neurons and astrocytes expre ss presenilin-1. Overall, it appears that the pattern of presenilin-1 gene expression parallels that previously described for the amyloid pr ecursor protein.