Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains.
Inflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Overexpression of tumor necrosis factor-α (TNF-α) occurs in the AD brain. Recent clinical studies have shown that the anti-TNF-α therapy improves cognition function of AD patients rapidly. However, the underlying mechanism remains elusive. The present study investigates the effects of intracerebroventricular injection of the monoclonal TNF-α antibody, Infliximab, on the pathological features of AD in the APP/PS1 double transgenic mice. We found that Infliximab administration reduced the levels of TNF-α, amyloid plaques, and tau phosphorylation as early as three days after daily injection of 150 μg Infliximab for three days. The number of CD11c-positive dendritic-like cells and the expression of CD11c were found to be increased concurrently after Infliximab injection. These data suggested that the CD11c-positive dendritic-like cells might contribute to the Infliximab-induced reduction of AD-like pathology. Furthermore, our results support the use of anti-TNF-α for the treatment of AD.
Shi
Jian-Quan
JQ
Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 210029, PR China. myxiyi_0717@hotmail.com
Shen
Wei
W
Chen
Jun
J
Wang
Bian-Rong
BR
Zhong
Ling-Ling
LL
Zhu
Yin-Wei
YW
Zhu
Hai-Qing
HQ
Zhang
Qiao-Quan
QQ
Zhang
Ying-Dong
YD
Xu
Jun
J
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D039521:CD11c Antigen / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D000069285:Infliximab; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects; D058225:Plaque, Amyloid / Q000188:drug therapy; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*; D016875:tau Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D039521:CD11c Antigen; D014409:Tumor Necrosis Factor-alpha; D016875:tau Proteins; D000069285:Infliximab