Synthetic amyloid-β oligomers drive early pathological progression of Alzheimer's disease in nonhuman primates.
Synthetic amyloid-β oligomers drive early pathological progression of Alzheimer's disease in nonhuman primates.
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合成淀粉样蛋白-β 寡聚体驱动非人类灵长类动物阿尔茨海默病的早期病理进展。
DOI：
10.1016/j.isci.2021.103207
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发表时间：
2021-10-22
期刊：
影响因子：
5.8
通讯作者：
Jing N
中科院分区：
文献类型：
--
作者：
Yue F;Feng S;Lu C;Zhang T;Tao G;Liu J;Yue C;Jing N
阿尔茨海默病（AD）是一种潜伏的、缓慢进展的神经退行性疾病，仅在人类中发病，但在其他物种中不起作用。因此，在动物（包括非人灵长类动物）中重建人类AD一直是一个挑战。在本研究中，我们将人工合成的Aβ低聚物（Aβ o）注入食蟹猴的脑实质，这迅速推动了大量Aβ斑块的形成和伴随的神经原纤维缠结在食蟹猴大脑中。a β o猴子的淀粉样蛋白和tau蛋白病理以及它们的共同出现与AD患者相似。此外，活化的星形胶质细胞和小胶质细胞周围的Aβ斑块提示触发的神经炎症。食蟹脑内也出现了Aβ斑块周围的退行性神经元和突触。综上所述，可溶性a β o在猴子中引起了与阿尔茨海默病相关的一系列病理事件，这些事件发生在患者的早期阶段，这可能有助于在非人类灵长类动物中建立一种有希望的人类阿尔茨海默病动物模型。Aβ寡聚物（Aβ o）驱动猴子脑内形成大量的Aβ斑块Aβ o猴的多个脑区形成神经原纤维缠结Aβ o猴的淀粉样蛋白和tau蛋白病理在AD患者中共同出现神经炎症和神经退行性变在Aβ o猴神经科学中触发；生物模型;合成生物学
As an insidious and slowly progressive neurodegenerative disorder, Alzheimer’s disease (AD) uniquely develops in humans but fails in other species. Therefore, it has been challenged to rebuild human AD in animals, including in non-human primates. Here, we bilaterally delivered synthetic Aβ oligomers (AβOs) into the cerebral parenchyma of cynomolgus monkeys, which rapidly drove the formation of massive Aβ plaques and concomitant neurofibrillary tangles in the cynomolgus brain. The amyloid and tau pathology as well as their co-occurrence in AβO-monkeys were reminiscent of those in patients with AD. In addition, the activated astrocytes and microglia surrounding Aβ plaques indicated the triggered neuroinflammation. The degenerative neurons and synapses around Aβ plaques also emerged in cynomolgus brain. Together, soluble AβOs caused the cascade of pathologic events associated with AD in monkeys as occurred in patients at the early phase, which could facilitate the development of a promising animal model for human AD in non-human primates. The Aβ oligomers (AβOs) drive to develop massive Aβ plaque in the monkey brain Neurofibrillary tangles form in multiple brain regions of AβO-monkeys The co-occurrence of amyloid and tau pathology in AβO-monkeys as in patients with AD The neuroinflammation and neurodegeneration are triggered in AβO-monkeys Neuroscience; Model organism; Synthetic biology
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.3
作者：
Brouillette, Jonathan;Caillierez, Raphaelle;Buee, Luc
通讯作者：
Buee, Luc
影响因子：
16.6
作者：
Kwak, Sang Su;Washicosky, Kevin J.;Kim, Doo Yeon
通讯作者：
Kim, Doo Yeon
影响因子：
82.9
作者：
Geula, C;Wu, CK;Yankner, BA
通讯作者：
Yankner, BA
DOI：
10.1073/pnas.0602896103
发表时间：
2006-06-06
影响因子：
11.1
作者：
Malm, Tarja;Ortt, Michael;Koistinaho, Jari
通讯作者：
Koistinaho, Jari