Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer's disease

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 aβ pathology; instead 8 months of hivig treatment significantly increased soluble levels of aβ40 and aβ42. 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-α 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. © 2012 puli et al.; licensee biomed central ltd.