Anna Papazoglou, Muhammad I. Arshaad, Christina Henseler, Johanna Daubner, Karl Broich, Britta Haenisch and Marco Weiergräber* Pages 453 - 469 ( 17 )
Early pharmacoepidemiological studies suggested that Proton Pump Inhibitors (PPIs) might increase the risk of Alzheimer’s Disease (AD) and non-AD related dementias. These findings were supported by preclinical studies, specifically stressing the proamyloidogenic and indirect anticholinergic effects of PPIs. However, further large-scale pharmacoepidemiological studies showed inconsistent results on the association between PPIs and dementia. Pharmacodynamically, these findings might be related to the LXR/RXR-mediated amyloid clearance effect and anti-inflammatory action of PPIs. Further aspects that influence PPI effects on AD are related to patient- specific pharmacokinetic and pharmacogenomic characteristics. In conclusion, a personalized (individualized) medicinal approach is necessary to model and predict the potential harmful or beneficial effects of PPIs in AD and non-AD-related dementias in the future.
Alzheimer's disease, dementia, LXR, pharmacodynamics, pharmacoepidemiology, pharmacogenomics, pharmacokinetics, PPARγ, proton pump inhibitor, RXR.
Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) 53127, Kurt-Georg- Kiesinger-Allee 3, 53175 Bonn, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) 53127, Kurt-Georg- Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn