Research

Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis

Yuemang Yao¹ , Cinzia Chinnici¹ , Hanguan Tang¹ , John Q Trojanowski^2,3 , Virginia MY Lee^2,3 and Domenico Praticò¹

¹  Center for Experimental Therapeutics and Department of Pharmacology; University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 USA

²  Center for Neurodegenerative Disease Research; University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 USA

³  Institute on Aging; University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 USA

author email corresponding author email

Journal of Neuroinflammation 2004, 1:21doi:10.1186/1742-2094-1-21

Published:	22 October 2004

Abstract

Background

An increasing body of evidence implicates both brain inflammation and oxidative stress in the pathogenesis of Alzheimer's disease (AD). The relevance of their interaction in vivo, however, is unknown. Previously, we have shown that separate pharmacological targeting of these two components results in amelioration of the amyloidogenic phenotype of a transgenic mouse model of AD-like brain amyloidosis (Tg2576).

Methods

In the present study, we investigated the therapeutic effects of a combination of an anti-inflammatory agent, indomethacin, and a natural anti-oxidant, vitamin E, in the Tg2576 mice. For this reason, animals were treated continuously from 8 (prior to Aβ deposition) through 15 (when Aβ deposits are abundant) months of age.

Results

At the end of the study, these therapeutic interventions suppressed brain inflammatory and oxidative stress responses in the mice. This effect was accompanied by significant reductions of soluble and insoluble Aβ1-40 and Aβ1-42 in neocortex and hippocampus, wherein the burden of Aβ deposits also was significantly decreased.

Conclusions

The results of the present study support the concept that brain oxidative stress and inflammation coexist in this animal model of AD-like brain amyloidosis, but they represent two distinct therapeutic targets in the disease pathogenesis. We propose that a combination of anti-inflammatory and anti-oxidant drugs may be a useful strategy for treating AD.