Brain inflammation and oxidative stress in a transgenic mouse model of Alzheimer-like brain amyloidosis.
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 Abeta deposition) through 15 (when Abeta 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 Abeta1-40 and Abeta1-42 in neocortex and hippocampus, wherein the burden of Abeta 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.
Yao
Yuemang
Y
Chinnici
Cinzia
C
Tang
Hanguan
H
Trojanowski
John Q
JQ
Lee
Virginia My
VM
Praticò
Domenico
D