Cortical iron regulation and inflammatory response in Alzheimer's disease and APPSWE/PS1ΔE9 mice: a histological perspective.
Cortical iron regulation and inflammatory response in Alzheimer's disease and APPSWE/PS1ΔE9 mice: a histological perspective.
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DOI：
10.3389/fnins.2015.00255
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发表时间：
2015
影响因子：
4.3
通讯作者：
Yang QX
中科院分区：
文献类型：
--
作者：
Meadowcroft MD;Connor JR;Yang QX
已知在阿尔茨海默病(AD)患者的大脑中会发生铁稳态的破坏和神经胶质反应的增强。虽然APP/PS1转基因小鼠模型重现了AD标志性的淀粉样β斑块病理，但它是在不同于人类的神经元中做到这一点的。在测试新的治疗程序和翻译这些结果时，了解APP/PS1模型的铁特性和胶质反应是重要的。对AD患者、APP/PS1小鼠和对照组的脑组织进行铁、H铁蛋白和L铁蛋白、小胶质细胞、星形胶质细胞、Aβ40/42和变性神经元的染色。组织学数据表明APP/PS1和AD组织在铁蛋白、铁分布、胶质增生和Aβ斑块组成方面存在差异。具体地说，局灶性铁沉积和Aβ斑块之间的关联在整个AD组织中普遍存在，在APP/PS1小鼠模型中没有观察到。在AD和APP/PS1组织中，铁蛋白、小胶质细胞和星形胶质细胞染色显示对淀粉样斑块的不同反应模式。β40和42抗体和硫代黄素染色显示斑块成分的形态差异。组织学数据支持这一假说，即APP/PS1和AD脑中铁的分布、铁的管理和神经胶质细胞的反应在组织学上是不同的。认识到AD大脑和APP/PS1鼠标之间有明显的斑块、铁和神经胶质对比是使用这一模型时至关重要的。
Disruption of iron homeostasis and increased glial response are known to occur in brains afflicted by Alzheimer's disease (AD). While the APP/PS1 transgenic mouse model recapitulates the hallmark amyloid-beta plaque pathology of AD, it does so in a different neuronal mileu than humans. Understanding the iron characteristics and glial response of the APP/PS1 model is important when testing new treatment procedures and translating these results. Brain tissue from AD patients, APP/PS1 mice, and controls were stained for iron, H- and L-ferritin, microglia, astrocytes, Aβ40∕42, and degenerating neurons. The histological data demonstrate differences in ferritin, iron distribution, gliosis, and Aβ plaque composition between APP/PS1 and AD tissue. Specifically, an association between focal iron deposition and Aβ plaques is found ubiquitously throughout the AD tissue and is not observed in the APP/PS1 mouse model. Ferritin, microglia, and astrocyte staining show differential response patterns to amyloid plaques in AD and the APP/PS1 tissue. Aβ 40 and 42 antibody and thioflavin staining demonstrate morphological differences in plaque composition. The histological data support the hypothesis that iron distribution, iron management, and glial response histologically differ between the APP/PS1 and AD brain. Acknowledging the caveat that there are distinct plaque, iron, and glial contrasts between the AD brain and the APP/PS1 mouse is crucial when utilizing this model.