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.
A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland. Lakshman.puli@uef.fi
Lakshman
L
Puli
Yuriy
Y
Pomeshchik
Katja
K
Olas
Tarja
T
Malm
Jari
J
Koistinaho
Heikki
H
Tanila
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D011897:Random Allocation; D016896:Treatment Outcome
D016756:Immunoglobulins, Intravenous