The presenilin-1 (PS-1) gene on chromosome 14 carries mutations which cosegregate with early-onset familial Alzheimer's disease. We quantified PS-1 mRNA in post-mortem mid-temporal and superior frontal cortices from 14 Alzheimer's disease subjects, 9 non-demented controls and 5 subjects with other neurological diseases using solution hybridisation-RNase protection assay. APP and APLP2 mRNAs had previously been quantified in these samples (Johnston et al. (1996) Mol. Brain Res., in press) and subjects were apolipoprotein E (APOE) genotyped. There were no significant differences between PS-1 mRNA levels per pg total RNA in mid-temporal or superior frontal cortices of the Alzheimer's disease subjects, compared to controls. PS-1 mRNA levels corresponded to 10% of total APP and 30% of APLP2 mRNA levels, and were not significantly affected by age, post-mortem delay, tissue pH, or APOE genotype. PS-1 mRNA showed significant positive correlations with APP and APLP2 mRNA levels in mid-temporal cortex and with APP mRNA in superior frontal cortex. This may reflect a co-regulation of the expression of these genes, or the fact that they are expressed in similar neuronal populations.