Expression of presenilin 1 in nervous system during rat development

Alzheimer's disease (AD) is a polygenic disorder involving at least four di fferent genes. Among them, missense mutations in the presenilins segregate with the vast majority of early onset cases of familial AD. To elucidate po ssible function(s) of presenilin I (PSI), we have studied its expression du ring the development of the rat nervous system. Analysis by in situ hybridi zation showed expression of PSI in a variety of cell types and tissues duri ng development, with prominent expression in the nervous system. During lat e embryogenesis, the ventricular zone presented the highest levels of expre ssion, paralleling the pattern previously reported for Notch. Later, during postnatal development, we observed a peak of PS1 expression at postnatal d ay 10, particularly in the cerebellum and hippocampus, a time when prolifer ation and migration are still ongoing and synapse formation is being comple ted. We propose that presenilins participate in at least two different deve lopmental processes: (1) one involved in neurogenesis and skeleton formatio n during embryonic development, probably involving coordinate expression wi th Notch, and (2) a second one in the postnatal central nervous system, per haps involved in neuritogenic and/or synaptogenic stages, most likely playi ng a role in amyloid precursor protein processing and amyloid beta producti on. (C) 1999 Wiley-Liss Inc.