Short-term treatment with tolfenamic acid improves cognitive functions in alzheimer's disease mice

Lina I. Adwan, Aseef H. Ahmed, Karen E. Stevens, Nasser H. Zawia

Research output: Contribution to journalJournal articlepeer-review

33 Scopus citations

Abstract

Tolfenamic acid lowers the levels of the amyloid precursor protein (APP) and amyloid beta (Aβ) when administered to C57BL/6 mice by lowering their transcriptional regulator specificity protein 1 (SP1). To determine whether changes upstream in the amyloidogenic pathway that forms Aβ plaques would improve cognitive outcomes, we administered tolfenamic acid for 34 days to hemizygous R1.40 transgenic mice. After the characterization of cognitive deficits in these mice, assessment of spatial learning and memory functions revealed that treatment with tolfenamic acid attenuated long-term memory and working memory deficits, determined using Morris water maze and the Y-maze. These improvements occurred within a shorter period of exposure than that seen with clinically approved drugs. Cognitive enhancement was accompanied by reduction in the levels of the SP1 protein (but not messenger RNA [mRNA]), followed by lowering both the mRNA and the protein levels of APP and subsequent Aβ levels. These findings provide evidence that tolfenamic acid can disrupt the pathologic processes associated with Alzheimer's disease (AD) and are relevant to its scheduled biomarker study in AD patients.

Original languageEnglish
Pages (from-to)2421-2430
Number of pages10
JournalNeurobiology of Aging
Volume34
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • AD transgenic mouse model
  • Alzheimer's disease
  • Learning and memory
  • Morris water maze
  • Tolfenamic acid
  • Y-maze

Fingerprint

Dive into the research topics of 'Short-term treatment with tolfenamic acid improves cognitive functions in alzheimer's disease mice'. Together they form a unique fingerprint.

Cite this