Presenilin 1 cleavage is a universal event in human organs

A panel of antibodies raised against various regions of human presenilin 1(PS1)-the amino-terminal domain, the domain between the transmembrane domains 1 and 2, the cleavage-site, loop domains, or carboxyl-terminal domain-was prepared to analyze PS1 in human tissues. We observed the predominance of two fragments (28-kDa NH2 and 18-kDa COOH fragments) in various tissues, including cerebral cortices. In addition to these two fragments, Lye found a previously unidentified amino-terminal fragment of PS 1 with Mr 14 kDa in the lungs, spleen, pancreas, and testes. Using a sensitive ELISA for PS 1, we measured the amount of PS 1 species in tissues and found high contents of PS1 fragment in the testes. Our data show that common and unique processing pathways of PS1 occur in a tissue-dependent manner. It is likely that cleavage al the loop structure of PS1 to produce a functional form is a common event in human organs. (C) 1998 Elsevier Science Inc.