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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 an...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416679/ https://www.ncbi.nlm.nih.gov/pubmed/22642812 http://dx.doi.org/10.1186/1742-2094-9-105 |
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author | Puli, Lakshman Pomeshchik, Yuriy Olas, Katja Malm, Tarja Koistinaho, Jari Tanila, Heikki |
author_facet | Puli, Lakshman Pomeshchik, Yuriy Olas, Katja Malm, Tarja Koistinaho, Jari Tanila, Heikki |
author_sort | Puli, Lakshman |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3416679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34166792012-08-11 Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease Puli, Lakshman Pomeshchik, Yuriy Olas, Katja Malm, Tarja Koistinaho, Jari Tanila, Heikki J Neuroinflammation Research 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. BioMed Central 2012-05-29 /pmc/articles/PMC3416679/ /pubmed/22642812 http://dx.doi.org/10.1186/1742-2094-9-105 Text en Copyright ©2012 Puli et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Puli, Lakshman Pomeshchik, Yuriy Olas, Katja Malm, Tarja Koistinaho, Jari Tanila, Heikki Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease |
title | Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease |
title_full | Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease |
title_fullStr | Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease |
title_full_unstemmed | Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease |
title_short | Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease |
title_sort | effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3416679/ https://www.ncbi.nlm.nih.gov/pubmed/22642812 http://dx.doi.org/10.1186/1742-2094-9-105 |
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