Abstract
Amyloid β protein precursor is cleaved by β- and γ-secretases to produce Aβ peptides which deposit in amyloid plaques in Alzheimer's disease (AD) brain. A recently identified beta-site cleaving enzyme (BACE) appears to fulfill the requirements for β-secretase, and presenilin-1 (PS1) appears to constitute the catalytic component of γ-secretase. Each protein has a close homologue (BACE2 and PS2, respectively), whose roles in AβPP cleavage remain uncertain. All four of these genes have been reported to be expressed in the human pancreas, but the cell types expressing these genes remains unknown. We demonstrate here the cell-specific expression of AβPP, BACE, BACE2, PS1, and PS2 in the human pancreas. The insulin-producing βcells were found to express AβPP, BACE and PS2 at high levels, and PS1 at a lower level. The other islet cell types expressed none of these five genes. By contrast, the exocrine ductal cells of the pancreas expressed AβPP and BACE2 selectively. These results suggest that secretase inhibitors under development for the treatment of AD, particularly those that target BACE, may have potential for adverse effects on pancreatic β cell function, and therefore glycemic control.