摘要
背景:甲醛(FA)在阿尔茨海默病(AD)的病理过程中被认为是一种与年龄有关的因素,也是一种蛋白交联剂,可在体外聚集淀粉样β(Aβ)和τ蛋白。在认知障碍严重的患者和AD患者的大脑中也发现了更高水平的FA。目的:探讨长期升高FA对灵长类脑AD病理标志物的影响。方法:幼龄恒河猴(5~8岁,无AD相关突变)给予慢性脑室内注射(i.c.v.)在12个月内注射FA或车辆。监测猴子认知能力的变化,并评估死亡后常见AD病理标记物的变化。结果:注射FA的猴有明显的空间工作记忆障碍。组织病理学分析显示,在接受i.c.v的猴脑区(海马、内嗅皮质和前额叶皮质)存在淀粉样-β神经元样斑块、神经原纤维缠结样形成、τ蛋白磷酸化增加、神经元丢失和反应性胶质化(AD)三种相关脑区(海马、内嗅皮质和前额叶皮质)。注射FA。酶联免疫吸附试验(ELISA)结果表明,FA处理的猴海马和PFC中pT 181和Aβ42含量显著升高。结论:FA可诱导幼龄恒河猴AD样主要病理标记物和认知障碍,且与遗传倾向无关。这表明FA可能在疾病的发生和发展中起重要作用。
关键词: 阿尔茨海默病,甲醛,聚集,神经性斑块,神经原纤维缠结,神经元丢失,反应性胶质疾病,猴子。
Current Alzheimer Research
Title:Alzheimer's Disease-Like Pathologies and Cognitive Impairments Induced by Formaldehyde in Non-Human Primates
Volume: 15 Issue: 14
关键词: 阿尔茨海默病,甲醛,聚集,神经性斑块,神经原纤维缠结,神经元丢失,反应性胶质疾病,猴子。
摘要: Background: Formaldehyde (FA) has been implicated in Alzheimer’s disease (AD) pathology as an age-related factor and as a protein cross-linker known to aggregate Amyloid-Beta (Aβ) and tau protein in vitro. Higher levels of FA have also been found in patients with greater cognitive impairment and in AD patient brains.
Objective: To directly evaluate the effect of chronically elevated FA levels on the primate brain with respect to AD pathological markers.
Method: Young rhesus macaques (5-8 yrs, without AD related mutations) were given chronic intracerebroventricular (i.c.v.) injections of FA or vehicle over a 12-month period. Monkeys were monitored for changes in cognitive ability and evaluated post-mortem for common AD pathological markers.
Results: Monkeys injected with FA were found to have significant spatial working memory impairments. Histopathological analysis revealed the presence of amyloid-β+ neuritic-like plaques, neurofibrillary tangle-like formations, increased tau protein phosphorylation, neuronal loss and reactive gliosis in three memory (and AD) related brain areas (the hippocampus, entorhinal cortex and prefrontal cortex (PFC)) of monkeys receiving i.c.v. injections of FA. ELISA assays revealed that the amounts of pT181 and Aβ42 were markedly higher in the PFC and hippocampus of FA treated monkeys.
Conclusion: FA was found to induce major AD-like pathological markers and cognitive impairments in young rhesus monkeys independent of genetic predispositions. This suggests FA may play a significant role in the initiation and progression of the disease.
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Cite this article as:
Alzheimer's Disease-Like Pathologies and Cognitive Impairments Induced by Formaldehyde in Non-Human Primates, Current Alzheimer Research 2018; 15 (14) . https://dx.doi.org/10.2174/1567205015666180904150118
DOI https://dx.doi.org/10.2174/1567205015666180904150118 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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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
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