PRESENILIN-1-IMMUNOREACTIVE NEURONS ARE PRESERVED IN LATE-ONSET ALZHEIMERS-DISEASE

Recent studies have suggested that missense mutations in the presenili n-1 gene are causally related to the majority of familial early-onset Alzheimer's disease (AD), To examine the possible involvement of prese nilin-1 in late-onset sporadic AD, a quantitative analysis of ifs dist ribution in the cerebral cortex of nondemented and AD patients was per formed using immunocytochemistry. Stereological analyses revealed that AD brains showed a marked neuronal loss in the CA1 field of the hippo campus and hilus of the dentate gyrus, subiculum, and entorhinal col-t ex. In these areas, however, the fraction of neurofibrillary tangle (N FT)-free neurons showing presenilin-1 immunoreactivity was increased c ompared with nondemented controls, In contrast, cortical areas, which displayed no neuronal loss, did not show any significant increase in t he fraction of presenilin-1-positive neurons. Moreover, presenilin-1 i mmunoreactivity was reduced in NFT-containing neurons, Thus, in AD, th e fraction of NFT-free neurons that contained pl presenilin-1 varied f rom 0.48 to 0.77, whereas the fraction of NFT-containing neurons that were presenilin-1 positive varied from 0.1 to 0.24. Together, these ob servations indicate that presenilin-1 may have a neuroprotective role ann that in AD low cellular expression of this protein may be associat ed with increased neuronal loss and NET formation.