Objective        To examine the expression and distribution of presenilin enhancer-2 (Pen-2)

an essential component of γ-secretase complex

in the brain of APP/PS1 double transgenic mice

so as to clarify the relationship between Pen-2 and Alzheimer’s disease (AD).       Methods      Offspring which were bred by APP/PS1 double transgenic AD mice were genotyped. Immunohistochemical staining was used to check the distribution and expression of Pen-2 in the brain of 8-month-old APP/PS1 double transgenic AD model mice and its age-matched wild-type littermates.       Results      Pen-2 was widely expressed throughout almost all the regions of brain in APP/PS1 double transgenic mice

including the cerebral cortex

hippocampus

basal nuclei

rhinencephalon

cerebellum

brainstem

and so on. While senile plaques (SP) were selectively distributed in the cerebral cortex

hippocampus

and rhinencephalon. The distribution of Pen-2 was much more extensive than that of SP in the brain of AD model mice. Meanwhile

Pen-2-positive neurons in AD model mice (2.09±0.33) was more dark-stained than that in wildtype controls (1.29±0.31); Furthermore

both the cell membrane and cytoplasm of Pen-2-positive neurons were heavily stained in the AD mice

while in the wildtype littermates

only membrane and its surrounding of Pen-2-positive neurons were relatively dark-stained

and the cytoplasma was mildly or not stained.       Conclusion        Distribution and expression of Pen-2  in the brain of APP/PS1 double transgenic mouse model is different from its wildtype littermates. These differences may indicate that Pen-2 is tightly related to SP formation and AD pathogenesis.