Abstract
The common pathological hallmark of Alzheimer’s disease (AD) is β-amyloid plaque deposition. The ideal therapy would reduce the Aβ burden with a low inflammatory immune response. Passive immunotherapy is an advanced treatment that dramatically reduces brain Aβ pathologies in AD animal models. The objective of our study was to observe the effects of 5C8H5, a novel monoclonal antibody derived from 4Aβ1-15, on brain Aβ pathology in an APP/PS1 mouse model of AD. Six-month-old transgenic mice were administered 5C8H5, 4Aβ1-15 or IgG, and same-aged wild-type untreated C57Bl/6J mice were employed as controls. Inflammatory factors and Aβ40/42 levels were detected by ELISA, while Aβ plaques, microglial cell activation, microhemorrhages and neurogenesis were evaluated by immunohistochemical staining. Compared with 4Aβ1-15-treated mice, the mice in the 5C8H5 group induced more Aβ clearance with less microglial cell activation in a niche of Th2-polarized immune response. The levels of proinflammatory factors, including IL-1β, IL-6, TNF-α and IFN-γ, were significantly decreased in the CNS, while the level of antiinflammatory IL-4 was increased. Moreover, the mice in the 5C8H5 group induced more neurogenesis without microhemorrhage exacerbation and thereby performed better in behavioral assays than did the 4Aβ1-15 group. In conclusion, the novel monoclonal antibody induces more Aβ clearance and less microglial cell activation in the absence of inflammation, accompanied by an increased Th2-polarized immune response, which makes it a more promising therapeutic strategy. These data provide evidence that passive immunity could alleviate pathologic Aβ alterations by modulating inflammation and should be pursued further for the treatment of AD.
Keywords: Alzheimer’s disease, behavior, β-amyloid, inflammatory factors, microglia activation, microhemorrhage liability, neurogenesis, neuroinflammation.
Current Alzheimer Research
Title:4Aβ1-15-Derived Monoclonal Antibody Reduces More Aβ Burdens and Neuroinflammation than Homologous Vaccine in APP/PS1 Mice
Volume: 12 Issue: 4
Author(s): Yuwei Zhang, Juntao Zou, Junhua Yang and Zhibin Yao
Affiliation:
Keywords: Alzheimer’s disease, behavior, β-amyloid, inflammatory factors, microglia activation, microhemorrhage liability, neurogenesis, neuroinflammation.
Abstract: The common pathological hallmark of Alzheimer’s disease (AD) is β-amyloid plaque deposition. The ideal therapy would reduce the Aβ burden with a low inflammatory immune response. Passive immunotherapy is an advanced treatment that dramatically reduces brain Aβ pathologies in AD animal models. The objective of our study was to observe the effects of 5C8H5, a novel monoclonal antibody derived from 4Aβ1-15, on brain Aβ pathology in an APP/PS1 mouse model of AD. Six-month-old transgenic mice were administered 5C8H5, 4Aβ1-15 or IgG, and same-aged wild-type untreated C57Bl/6J mice were employed as controls. Inflammatory factors and Aβ40/42 levels were detected by ELISA, while Aβ plaques, microglial cell activation, microhemorrhages and neurogenesis were evaluated by immunohistochemical staining. Compared with 4Aβ1-15-treated mice, the mice in the 5C8H5 group induced more Aβ clearance with less microglial cell activation in a niche of Th2-polarized immune response. The levels of proinflammatory factors, including IL-1β, IL-6, TNF-α and IFN-γ, were significantly decreased in the CNS, while the level of antiinflammatory IL-4 was increased. Moreover, the mice in the 5C8H5 group induced more neurogenesis without microhemorrhage exacerbation and thereby performed better in behavioral assays than did the 4Aβ1-15 group. In conclusion, the novel monoclonal antibody induces more Aβ clearance and less microglial cell activation in the absence of inflammation, accompanied by an increased Th2-polarized immune response, which makes it a more promising therapeutic strategy. These data provide evidence that passive immunity could alleviate pathologic Aβ alterations by modulating inflammation and should be pursued further for the treatment of AD.
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Cite this article as:
Zhang Yuwei, Zou Juntao, Yang Junhua and Yao Zhibin, 4Aβ1-15-Derived Monoclonal Antibody Reduces More Aβ Burdens and Neuroinflammation than Homologous Vaccine in APP/PS1 Mice, Current Alzheimer Research 2015; 12 (4) . https://dx.doi.org/10.2174/1567205012666150325183708
DOI https://dx.doi.org/10.2174/1567205012666150325183708 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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