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

Ann C. McKee, Isabel Carreras, Lokman Hossain, Hoon Ryu, William L. Klein, Salvatore Oddo, Frank M. LaFerla, Bruce G. Jenkins, Neil W. Kowall, Alpaslan Dedeoglu

Research output: Contribution to journalArticle

168 Scopus citations

Abstract

We examined the effects of ibuprofen on cognitive deficits, Aβ and tau accumulation in young triple transgenic (3xTg-AD) mice. 3xTg-AD mice were fed ibuprofen-supplemented chow between 1 and 6 months. Untreated 3xTg-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 3xTg-AD mice was significantly improved with ibuprofen treatment compared to untreated 3xTg-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 3xTg-AD mice. Our findings show that prophylactic treatment of young 3xTg-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.

Original languageEnglish (US)
Pages (from-to)225-236
Number of pages12
JournalBrain Research
Volume1207
DOIs
StatePublished - May 1 2008

Keywords

  • Alzheimer
  • Amyloid
  • Cognitive test
  • Ibuprofen
  • Immunohistochemistry
  • Tau
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    McKee, A. C., Carreras, I., Hossain, L., Ryu, H., Klein, W. L., Oddo, S., LaFerla, F. M., Jenkins, B. G., Kowall, N. W., & Dedeoglu, A. (2008). Ibuprofen reduces Aβ, hyperphosphorylated tau and memory deficits in Alzheimer mice. Brain Research, 1207, 225-236. https://doi.org/10.1016/j.brainres.2008.01.095