摘要
阿兹海默症(AD)常见的病理学标志是淀粉样β蛋白斑块沉积。理想的治疗方法是减少Aβ负担并伴随低炎症免疫反应。被动免疫疗法是一种先进的治疗方式可以显著减少AD动物模型大脑中Aβ病状。我们研究的目的是观察5C8H5对AD模型APP / PS1小鼠大脑中Aβ的病理学影响,5C8H5是一种新颖的单克隆抗体,是4Aβ1-15的衍生物。治疗组对6月龄转基因小鼠使用5C8H5, 4Aβ1-15 或 IgG,同龄野生未处理C57Bl/6J 小鼠作为对照组。酶联免疫法(ELISA)测定炎性因子和Aβ40/42水平,免疫组化染色评价Aβ斑块、小胶质细胞激活、微出血和神经发生。与4Aβ1-15组小鼠相比,5C8H5组小鼠在 Th2-极化免疫反应的微环境中引发了更多的Aβ清除和更少的小胶质细胞激活。炎性因子水平,包括 IL-1β、 IL-6、 TNF-α 和 IFN-γ,在中枢神经系统(CNS)中明显降低,抗炎因子IL-4水平增高。此外,5C8H5组小鼠神经发生减少,无微出血加重,因此行为学测试表现好于4Aβ1-15组小鼠。总之,这种新颖的单克隆抗体在无炎症反应伴随 Th2-极化免疫反应中,引发了更多的Aβ清除和更少的小胶质细胞激活,使其成为更有前景的治疗策略。这些数据为被动免疫疗法可以通过调节炎性反应来减少病理性Aβ改变提供了证据,应该进一步寻求治疗AD的方法。
关键词: 阿兹海默症,行为,β-淀粉样蛋白,炎性因子,小神经胶质细胞激活,微出血倾向,神经发生,神经炎症。
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:
关键词: 阿兹海默症,行为,β-淀粉样蛋白,炎性因子,小神经胶质细胞激活,微出血倾向,神经发生,神经炎症。
摘要: 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:
Yuwei Zhang, Juntao Zou, Junhua Yang and Zhibin Yao , 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 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
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