期刊
JOURNAL OF NEUROINFLAMMATION
卷 9, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1742-2094-9-105
关键词
Human intravenous immunoglobulin; Amyloid pathology; Microglia; Neuroinflammation; Alzheimer's disease
资金
- Baxter innovations GmbH
- Baxter A/G, Austria
- Marie curie ESTBiND Program
- EC [MEST-CT-2005-19217]
- North-Savonia Regional Foundation
Background: Human intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural anti-amyloid beta antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial effects to patients of Alzheimer's disease (AD). Here, we set out to explore the effects of hIVIG in a mouse model of AD. Methods: We treated APP/PS1dE9 transgenic and wild-type mice with weekly injections of a high hIVIG dose (1 g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR, and confocal microscopy. Results: We found no evidence for reduction in A beta pathology; instead 8 months of hIVIG treatment significantly increased soluble levels of A beta 40 and A beta 42. In addition, we noticed a significant reduction in CD45 and elevation of Iba-1 markers in specific sub-populations of microglial cells. Long-term hIVIG treatment also resulted in significant suppression of TNF-alpha and increase in doublecortin positive adult-born neurons in the dentate gyrus. Conclusions: Our data indicate limited ability of hIVIG to impact amyloid burden but shows changes in microglia, pro-inflammatory gene expression, and neurogenic effects. Immunomodulation by hIVIG may account for its beneficial effect in AD patients.
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