Missense mutations of the S182 gene (presenilin 1) in chromosome 14 and STM2 gene (presenilin 2) in chromosome 1 are causative of some of autosomal dominant familial Alzheimer's disease. They are believed to have an important role on APP processing. For the first step to understand the function of presenilin and the relationship to amyloid Aβ formation, we investigated histochemical localization of presenilin in human brain. Antibodies were produced against six synthesized peptides corresponding to the hydrophilic domains including N- and C-termini of presenilin 1, in which three of them are presenilin 1 specific and other three can also react to presenilin 2. These antibodies commonly recognized 49 kDa protein(s) by Western blot and immunoprecipitation. Forty-nine kDa protein(s) were predominantly present in the cytosol fraction (supernatant of 105 k x g) of the brain homogenate. Immunohistochemically, the staining product was seen in both astrocytes and neurons, and less extent in senile plaques. The most prominent staining was in the end-feet, coarse and fine processes and cytoplasm of astrocytes. In neurons, the staining was seen in granules, particularly in large pyramidal neurons, but negative in axons. The staining pattern and intensity were not different in the brains of Alzheimer's disease and other neurological disease. These findings suggest that presenilin is most probably involved in intracellular or transcytic transport of certain substances.This work was supported by grants from Science and Technology Agency (COE), and Ministry of Health and Welfare (Aging and Health) of Japan.