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R-flurbiprofen improves axonal transport in the Tg2576 mouse model of Alzheimer's disease as determined by MEMRI


Year of Publication:
Contact PI Name:
Pautler G. Robia
Contact PI Affiliation:
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, USA
Karen D.B. Smith, Richard Paylor
Primary Reference (PubMED ID):
Funding Source:
National Institute on Aging (NIA)
National Heart Lung and Blood Institute (NHLBI)
Study Goal and Principal Findings:

This study investigated effects of R-flurbiprofen (R-F) on axonal transport and AD neuropathology in Tg2576 mice. Axonal pathology is thought to be a major contributor to AD pathology, and histological analyses of AD tissue from humans and transgenic mouse models indicate that axonal swellings likely precede synaptic deficits and could be an early indicator of AD. R-F is an enantiomer of the NSAID flurbiprofen capable of reducing Aβ42. The R-F isoform has been shown to have a COX-2 independent pathway of reducing pain without the gastrointestinal side effects associated with traditional COX-2 inhibiting NSAIDs. Currently, R-F also is thought to modulate the γ-secretase cleavage of Aβ42 to a shorter, less toxic peptide. In this study using Manganese Enhanced MRI (MEMRI), axonal transport deficits occur before plaque formation in Tg2576 mice. Results demonstrated that in young animals (before Aβ plaque formation), R-F treatment reduced Aβ42 levels and coincided with a significant improvement in axonal transport. However, in older animals (after plaque formation had occurred), R-F treatment did not reduce Aβ42 levels although there was a significant improvement in axonal transport as assessed with MEMRI. R-F treatment reduced tau hyperphosphorylation in the older animals. These data indicate that both Aβ42 and tau comprise a role in axonal transport rate deficits in the Tg2576 models.hyperphosphorylation in the older animals. These data indicate that both Aβ42 and tau comprise a role in axonal transport rate deficits in the Tg2576 models.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
gamma Secretase
Therapeutic Notes:
R-Flurbiprofen is the R-enantiomer of the NSAID Flurbiprofen. It is not a cyclooxygenase (COX 1/COX 2) inhibitor. R-Flurbiprofen has recently been shown to modulate gamma secretase and selectively lower levels of Aβ42 and amyloid pathology in vivo. R-Flurbiprofen also modulates NFκB signaling pathways.

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Model Type:
Strain/Genetic Background:

Experimental Design

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


Outcome Measured
Outcome Parameters
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
Total Tau Protein
Manganese Enhanced MRI (MEMRI)
Target Engagement (Reduction beta Amyloid Peptide 42-Brain)