IMMUNOHISTOCHEMICAL ANALYSIS OF PRESENILIN-1 EXPRESSION IN THE MOUSE-BRAIN

At least 22 different mutations associated with early-onset familial A lzheimer's disease (AD) in various kindreds have been reported to occu r in a recently identified gene on chromosome 14, presenilin 1 (PS-1) (Sherrington et al. (1995) Nature 375, 754-760 [I] and reviewed by Van Broeckhoven (1995) Nat, Genet, 11, 230-231 [2]). In order to study th e localization of PS-1 in the brain, we raised a polyclonal antiserum specific to a fragment of the predicted protein sequence of PS-1, PS-1 immunostaining was found intracellularly, in the perikaria of discret e cells, mostly neurons, appearing as thick granules, resembling large -size vesicles. These granules were located in the periphery of cell b odies and extended into dendrites and neurites. PS-1 expression was fo und to be broadly distributed throughout the mouse brain, not only in structures involved in AD pathology, but also in structures unaltered by this disease.