Decreased secretion of amyloid precursor protein in Chinese hamster ovary cells overexpressing presenilin 1

Mutations in the presenilin 1 (PS1) gene account for at least 50% of all early-onset familiar Alzheimer's disease cases. PS1 mutations have been associated with the increased production of the longer form of beta-amyloid (A beta(1-42)) indicating that PS1 may modulate amyloid precursor protein (APP) processing. In this study, Chinese hamster ovary (CHO) cells were stably transfected with native human PS1 cDNA and selected PS1 clones were isolated. Increased expression of the 28 kDa N-terminus of PS1 in transfected CHO cells, relative to mock-treated CHO cells, was demonstrated using immunoblotting techniques. Differences in PS1 expression levels in the clones were associated with changes in APP maturation and secretion. With increasing PS1 levels APP maturation was enhanced resulting in decreased secretion of total and alpha-cut APP. This decreased secretion of APP indicates that PS1 regulates intracellular trafficking of APP. We conclude that PS1 may play a role in directing APP to an intracellular processing pathway. Our data support the view that PS1 regulates APP metabolism.