Alzheimer’s disease (AD) is characterized by the accumulation in the brain of intraneuronal aggregates of abnormally and hyperphosphorylated tau proteins and of extracellular deposits of amyloid-β surrounded by dystrophic neurites. Numerous experimental models have shown that tau pathology develops in the brain after intracerebral injection of brain homogenates or pathological tau [paired helical filaments (PHF)-tau)] from AD brains. Further investigations are however necessary to identify or exclude potential extracerebral routes of tau pathology transmission, e.g., through the intravascular route. In this study, we have analyzed the effect of intravenous injection of PHF-tau proteins from AD brains on the formation of tau and amyloid pathologies in the brain of wild-type (WT) mice and of 5XFAD mice (an amyloid model). We observed that 5XFAD mice with a disrupted blood–brain barrier showed increased plaque-associated astrogliosis, microgliosis, and increased deposits of Aβ40 and Aβ42 after intravenous injection of PHF-tau proteins. In addition, an increased phosphotau immunoreactivity was observed in plaque-associated dystrophic neurites. These results suggest that blood products contaminated by PHF-tau proteins could potentially induce an exacerbation of neuroinflammation and AD pathologies.

阿尔茨海默氏病（AD）的特征是异常磷酸化和过磷酸化的tau蛋白在神经元内聚集在大脑中的聚集，以及被营养不良的神经突包围的β-淀粉样蛋白的细胞外沉积。许多实验模型表明，在脑内注射AD大脑的脑匀浆或病理性tau（成对的螺旋丝（PHF）-tau）后，tau病理在大脑中发展。但是，需要进一步的研究来确定或排除tau病理传播的潜在脑外途径，例如通过血管内途径。在这项研究中，我们分析了从AD脑中静脉注射PHF-tau蛋白对野生型（WT）小鼠和5XFAD小鼠（淀粉样蛋白模型）的脑中tau和淀粉样蛋白病理形成的影响。我们观察到，血脑屏障破坏的5XFAD小鼠静脉注射PHF-tau蛋白后，斑块相关性星形胶质增生，微胶质增生和Aβ40和Aβ42的沉积增加。另外，在斑块相关的营养不良性神经突中观察到磷酸化的免疫反应性增加。这些结果表明，受PHF-tau蛋白污染的血液制品可能会导致神经炎症和AD病理加剧。