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.