Ibuprofen reduces Aβ, hyperphosphorylated tau and memory deficits in Alzheimer mice


Year of Publication: 
Contact PI Name: 
Alpaslan Dedeoglu
Contact PI Affiliation: 
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA
Ann C. McKee, Isabel Carreras, Lokman Hossain, Hoon Ryu, William L. Klein, Salvatore Oddo, Frank M. LaFerla, Bruce G. Jenkins, Neil W. Kowall
Primary Reference (PubMED ID): 
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Study Goal and Principal Findings: 

This study examined the effects of ibuprofen on cognitive deficits, Aβ and tau accumulation in young triple transgenic (3×Tg-AD) mice. 3×Tg-AD mice were fed ibuprofen-supplemented chow between 1 and 6 months. Untreated 3×Tg-AD mice showed significant impairment in the ability to learn the Morris water maze (MWM) task compared to age-matched wild-type (WT) mice. The performance of 3×TgAD mice was significantly improved with ibuprofen treatment compared to untreated 3×Tg-AD mice. Ibuprofen-treated transgenic mice showed a significant decrease in intraneuronal oligomeric Aβ and hyperphosphorylated tau (AT8) immunoreactivity in the hippocampus. Confocal microscopy demonstrated co-localization of conformationally altered (MC1) and early phosphorylated tau (CP-13) with oligomeric Aβ, and less co-localization of oligomeric Aβ and later forms of phosphorylated tau (AT8 and PHF-1) in untreated 3×Tg-AD mice. These findings show that prophylactic treatment of young 3×Tg-AD mice with ibuprofen reduces intraneuronal oligomeric Aβ, reduces cognitive deficits, and prevents hyperphosphorylated tau immunoreactivity. These findings provide further support for intraneuronal Aβ as a cause of cognitive impairment, and suggest that pathological alterations of tau are associated with intraneuronal oligomeric Aβ accumulation. 

Therapeutic Agent

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Animal Model

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Experimental Design

Is the following information reported in the study?: 
Power/Sample Size Calculation
Blinded for Treatment
Pharmacokinetic Measures
Toxicology Measures
Duration of Treatment
Age of Animal at the Beginning of Treatment
Sex as a Biological Variable
Number of Premature Deaths
Statistical Plan
Inclusion/Exclusion Criteria Included
Randomized into Groups
Blinded for Outcome Measures
Pharmacodynamic Measures
ADME Measures
Route of Delivery
Frequency of Administration
Age of Animal at the End of Treatment
Study Balanced for Sex as a Biological Variable
Number of Excluded Animals
Genetic Background
Conflict of Interest


Outcome MeasuredOutcome Parameters
  • Morris Water Maze
  • Histopathology
  • Neurofibrillary Tau Tangles
  • Fibrillar beta Amyloid Deposits
  • Dense-core/Compact Plaques
  • phospho-Tau
  • Immunochemistry
  • Brain-beta Amyloid Oligomers
  • phospho-Tau
  • Tau Protein
  • Brain-beta Amyloid Peptides