输注具有脑淀粉样变性的小鼠血液可加速阿尔茨海默病动物模型中的淀粉样蛋白病理。
Infusion of blood from mice displaying cerebral amyloidosis accelerates amyloid pathology in animal models of Alzheimer's disease.
机构信息
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, The University of Texas Medical School at Houston, Houston, TX, 77030, USA.
Centro Integrativo de Biología y Química Aplicada (CIBQA), Universidad Bernardo O'Higgins, Santiago, Chile.
出版信息
Acta Neuropathol Commun. 2020 Dec 7;8(1):213. doi: 10.1186/s40478-020-01087-1.
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.
先前的研究表明,通过朊病毒样机制,注射含有淀粉样蛋白-β(Aβ)聚集物的组织提取物会加速阿尔茨海默病(AD)小鼠模型中大脑的淀粉样蛋白沉积。在这项研究中,我们评估了血液输注是否会加速脑淀粉样变性,因为这些程序已被证明会在动物和人类中传播朊病毒疾病。与未治疗的动物或输注野生型血液的小鼠相比,输注来自大脑中有大量 Aβ 沉积的老年动物的全血或血浆的年轻转基因小鼠,其大脑中的淀粉样蛋白沉积和神经炎症水平显著升高。同样,静脉内注射纯化的 Aβ 聚集物加速了淀粉样蛋白病理,支持了血液中存在的 Aβ 种子可以到达大脑,从而促进接受治疗的动物大脑中神经病理改变的概念。然而,不能排除供体血液中其他因素的淀粉样蛋白增强作用。我们的结果可能有助于理解外周(淀粉样蛋白依赖或不依赖)因素在 AD 发展中的作用,并揭示疾病干预的新策略。