合成Aβ寡聚体诱导非人灵长类动物阿尔茨海默病的早期病理进展

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，但在其他物种中不发病。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。本研究中，我们将人工合成的Ab寡聚物(AβOs)注入食蟹猴的脑实质，迅速推动了大量Aβ斑块的形成，并在食蟹猴脑内伴随神经原纤维缠结。AβO型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患者的相似。此外，Aβ斑块周围激活的星形胶质细胞和小胶质细胞提示触发的神经炎症。在食蟹脑中，Ab斑块周围也出现了退行性神经元和突触。总之，可溶性AβO在猴子中引起了与阿尔茨海默病相关的一系列病理事件，就像在患者早期发生的那样，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。

Alzheimer's disease (AD) is an insidious, slowly progressive neurodegenerative disorder that exclusively affects humans and has not been identified in other species. Therefore, reconstructing human AD in animals, including non-human primates, has long been a challenge. In this study, we injected synthetic amyloid-beta oligomers (AβOs) into the brain parenchyma of cynomolgus monkeys, which rapidly induced the formation of abundant Aβ plaques accompanied by neurofibrillary tangles in the monkey brains. The amyloid and tau pathologies in AβO-treated monkeys, as well as their co-occurrence, are highly similar to those observed in AD patients. Furthermore, activated astrocytes and microglia surrounding Aβ plaques indicate triggered neuroinflammation. Degenerating neurons and synapses were also observed around Aβ plaques in the cynomolgus monkey brains. Collectively, soluble AβOs induced a series of AD-associated pathological events in monkeys, mirroring those occurring in the early stages of human AD patients, which may facilitate the establishment of a promising animal model of human Alzheimer's disease in non-human primates.