No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer's disease

Antje Hillmann; Stefanie Hahn; Stephan Schilling; Torsten Hoffmann; Hans-Ulrich Demuth; Bruno Bulic; Thomas Schneider-Axmann; Thomas A Bayer; Sascha Weggen; Oliver Wirths

doi:10.1016/j.neurobiolaging.2011.08.006

No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimer's disease

Neurobiol Aging. 2012 Apr;33(4):833.e39-50. doi: 10.1016/j.neurobiolaging.2011.08.006. Epub 2011 Sep 22.

Authors

Antje Hillmann¹, Stefanie Hahn, Stephan Schilling, Torsten Hoffmann, Hans-Ulrich Demuth, Bruno Bulic, Thomas Schneider-Axmann, Thomas A Bayer, Sascha Weggen, Oliver Wirths

Affiliation

¹ Division of Molecular Psychiatry and Alzheimer Ph.D. Graduate School, Department of Psychiatry, University Medicine Goettingen, Goettingen, Germany.

PMID: 21943956
DOI: 10.1016/j.neurobiolaging.2011.08.006

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Alzheimer Disease / complications
Alzheimer Disease / drug therapy*
Alzheimer Disease / genetics
Alzheimer Disease / physiopathology
Amyloid beta-Peptides / genetics
Amyloid beta-Peptides / metabolism
Amyloid beta-Peptides / pharmacology
Amyloid beta-Protein Precursor / genetics
Animals
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
CHO Cells / drug effects
CHO Cells / metabolism
Calcium-Binding Proteins / metabolism
Chemokine CCL2 / metabolism
Cricetinae
Cytokines / genetics
Cytokines / metabolism
Disease Models, Animal
Encephalitis / etiology
Encephalitis / prevention & control*
Enzyme-Linked Immunosorbent Assay / methods
Exploratory Behavior / drug effects
Gene Expression Regulation / drug effects
Glial Fibrillary Acidic Protein / metabolism
Humans
Ibuprofen / therapeutic use*
Maze Learning / drug effects
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microfilament Proteins / metabolism
Mutation / genetics
Peptide Fragments / pharmacology
Presenilin-1 / genetics
Psychomotor Performance / drug effects
TATA-Box Binding Protein / genetics
TATA-Box Binding Protein / metabolism
Transfection

Substances

Aif1 protein, mouse
Amyloid beta-Peptides
Amyloid beta-Protein Precursor
Anti-Inflammatory Agents, Non-Steroidal
Calcium-Binding Proteins
Ccl2 protein, mouse
Chemokine CCL2
Cytokines
Glial Fibrillary Acidic Protein
Microfilament Proteins
PSEN1 protein, human
Peptide Fragments
Presenilin-1
TATA-Box Binding Protein
amyloid beta-protein (1-42)
Ibuprofen