The Proton-Pump Inhibitor Lansoprazole Enhances Amyloid Beta Production

A key event in the pathogenesis of Alzheimer's disease (AD) is the accumulation of amyloid-beta (A beta) species in the brain, derived from the sequential cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. Based on a systems biology study to repurpose drugs for AD, we explore the effect of lansoprazole, and other proton-pump inhibitors (PPIs), on Ab production in AD cellular and animal models. We found that lansoprazole enhances A beta 37, A beta 40 and A beta 42 production and lowers A beta 38 levels on amyloid cell models. Interestingly, acute lansoprazole treatment in wild type and AD transgenic mice promoted higher A beta 40 levels in brain, indicating that lansoprazole may also exacerbate Ab production in vivo. Overall, our data presents for the first time that PPIs can affect amyloid metabolism, both in vitro and in vivo.