Triflusal reduces dense-core plaque load, associated axonal alterations and inflammatory changes, and rescues cognition in a transgenic mouse model of Alzheimer's disease

M. Coma, L. Serenó, B. Da Rocha-Souto, T. C. Scotton, J. España, M. B. Sánchez, M. Rodríguez, J. Agulló, C. Guardia-Laguarta, M. Garcia-Alloza, L. A. Borrelli, J. Clarimón, A. Lleó, B. J. Bacskai, C. A. Saura, B. T. Hyman, T. Gómez-Isla

Research output: Contribution to journalArticleResearchpeer-review

32 Citations (Scopus)

Abstract

Inflammation has been associated with the two classic lesions in the Alzheimer's (AD) brain, amyloid deposits and neurofibrillary tangles. Recent data suggest that Triflusal, a compound with potent anti-inflammatory effects in the central nervous system in vivo, might delay the conversion from amnestic mild cognitive impairment to a fully established clinical picture of dementia. In the present study, we investigated the effect of Triflusal on brain Aβ accumulation, neuroinflammation, axonal curvature and cognition in an AD transgenic mouse model (Tg2576). Triflusal treatment did not alter the total brain Aβ accumulation but significantly reduced dense-cored plaque load and associated glial cell proliferation, proinflammatory cytokine levels and abnormal axonal curvature, and rescued cognitive deficits in Tg2576 mice. Behavioral benefit was found to involve increased expression of c-fos and BDNF, two of the genes regulated by CREB, as part of the signal transduction cascade underlying the molecular basis of long-term potentiation. These results add preclinical evidence of a potentially beneficial effect of Triflusal in AD. © 2010 Elsevier Inc.
Original languageEnglish
Pages (from-to)482-491
JournalNeurobiology of Disease
Volume38
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Alzheimer's disease
  • Amyloid
  • BDNF
  • C-fos
  • CREB
  • Cognition
  • Cytokines
  • Neuroinflammation
  • Transgenic mice
  • Triflusal

Fingerprint Dive into the research topics of 'Triflusal reduces dense-core plaque load, associated axonal alterations and inflammatory changes, and rescues cognition in a transgenic mouse model of Alzheimer's disease'. Together they form a unique fingerprint.

Cite this