Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer's disease

输入患有脑淀粉样变性的小鼠的血液会加速阿尔茨海默病动物模型中的淀粉样蛋白病理

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作者:Rodrigo Morales, Claudia Duran-Aniotz, Javiera Bravo-Alegria, Lisbell D Estrada, Mohammad Shahnawaz, Ping-Ping Hu, Carlos Kramm, Diego Morales-Scheihing, Akihiko Urayama, Claudio Soto

Abstract

Previous studies showed that injection of tissue extracts containing amyloid-β (Aβ) aggregates accelerate amyloid deposition in the brain of mouse models of Alzheimer's disease (AD) through prion-like mechanisms. In this study, we evaluated whether brain amyloidosis could be accelerated by blood infusions, procedures that have been shown to transmit prion diseases in animals and humans. Young transgenic mice infused with whole blood or plasma from old animals with extensive Aβ deposition in their brains developed significantly higher levels brain amyloidosis and neuroinflammation compared to untreated animals or mice infused with wild type blood. Similarly, intra-venous injection of purified Aβ aggregates accelerated amyloid pathology, supporting the concept that Aβ seeds present in blood can reach the brain to promote neuropathological alterations in the brain of treated animals. However, an amyloid-enhancing effect of other factors present in the blood of donors cannot be discarded. Our results may help to understand the role of peripheral (amyloid-dependent or -independent) factors implicated in the development of AD and uncover new strategies for disease intervention.

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