title: No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer's disease.
abstract: Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has been reported to reduce the risk of developing Alzheimer's disease (AD). Its preventive effects in AD are likely pleiotropic as ibuprofen displays both anti-inflammatory activity by inhibition of cyclooxygenases and anti-amyloidogenic activity by modulation of γ-secretase. In order to study the anti-inflammatory properties of ibuprofen independent of its anti-amyloidogenic activity, we performed a long-term treatment study with ibuprofen in 5XFAD mice expressing a presenilin-1 mutation that renders this AD model resistant to γ-secretase modulation. As expected, ibuprofen treatment for 3 months resulted in a reduction of the inflammatory reaction in the 5XFAD mouse model. Importantly, an unchanged amyloid beta (Aβ) plaque load, an increase in soluble Aβ42 levels, and an aggravation of some behavioral parameters were noted, raising the question whether suppression of inflammation by nonsteroidal anti-inflammatory drug is beneficial in AD.
authors.affiliation: Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Hillmann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hahn
authors.forename: Stephan
authors.initials: S
authors.lastname: Schilling
authors.forename: Torsten
authors.initials: T
authors.lastname: Hoffmann
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
authors.forename: Bruno
authors.initials: B
authors.lastname: Bulic
authors.forename: Thomas
authors.initials: T
authors.lastname: Schneider-Axmann
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bayer
authors.forename: Sascha
authors.initials: S
authors.lastname: Weggen
authors.forename: Oliver
authors.initials: O
authors.lastname: Wirths
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D006224:Cricetinae; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000494:pharmacology; D053764:Presenilin-1 / Q000235:genetics; D011597:Psychomotor Performance / Q000187:drug effects; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C491049:Aif1 protein, mouse; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002135:Calcium-Binding Proteins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D035181:TATA-Box Binding Protein; C075222:amyloid beta-protein (1-42); D007052:Ibuprofen