Bibliographic
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.