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Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer's Disease? Molecular Mechanisms and Clinical Implications

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Proton-pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole, are used for the treatment of gastroesophageal reflux disease and peptic ulcer disease. The use of PPIs has increased, especially in older individuals, and a pharmacoepidemiological study indicated the use of PPIs peaks in people aged 80 years or older. In this population, Alzheimer's disease (AD) is a common neurological disorder and type of dementia, occurring with a frequency of approximately 10%. Currently, over 45 million people are estimated to have dementia worldwide, and it is a major cause of death in the elderly. Recent clinical studies have indicated that chronic use of PPIs can be a risk factor for increased incidence of dementia, including AD. Potential molecular mechanisms related to the pathophysiology of AD (e.g., modulation of amyloid protein processing) have also been reported in both in vitro and in vivo studies. Although the clinical implications of these results are inconclusive, a literature review of the current knowledge is important for future basic and clinical research. This review summarizes the possible mechanisms connecting the use of PPIs and the incidence of AD. Additionally, we summarize results from clinical studies to highlight the influence in humans.
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Keywords: Alzheimer's disease; Proton pump inhibitor; clinical study; molecular mechanisms; neurodegenerative diseases; structure- activity relationships

Document Type: Review Article

Publication date: June 1, 2018

This article was made available online on February 20, 2018 as a Fast Track article with title: "Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer’s Disease? Molecular Mechanisms and Clinical Implications".

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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