Little is known about the effects of parenchymal or vascular amyloid β peptide (Aβ) deposition in the brain. We hypothesized that Aβ strain-specific information defines whether Aβ deposits on the brain parenchyma or blood vessels. We investigated 12 autopsied patients with different severities of Aβ plaques and cerebral amyloid angiopathy (CAA), and performed a seeding study using an Alzheimer’s disease (AD) mouse model in which brain homogenates derived from the autopsied patients were injected intracerebrally. Based on the predominant pathological features, we classified the autopsied patients into four groups: AD, CAA, AD + CAA, and less Aβ. One year after the injection, the pathological and biochemical features of Aβ in the autopsied human brains were not preserved in the human brain extract-injected mice. The CAA counts in the mice injected with all four types of human brain extracts were significantly higher than those in mice injected with PBS. Interestingly, parenchymal and vascular Aβ depositions were observed in the mice that were injected with the human brain homogenate from the less Aβ group. The Aβ and CAA seeding activities, which had significant positive correlations with the Aβ oligomer ratio in the human brain extracts, were significantly higher in the human brain homogenate from the less Aβ group than in the other three groups. These results indicate that exogenous Aβ seeds from different Aβ pathologies induced Aβ deposition in the blood vessels rather than the brain parenchyma without being influenced by Aβ strain-specific information, which might be why CAA is a predominant feature of Aβ pathology in iatrogenic transmission cases. Furthermore, our results suggest that iatrogenic transmission of Aβ pathology might occur due to contamination of brain tissues from patients with little Aβ pathology, and the development of inactivation methods for Aβ seeding activity to prevent iatrogenic transmission is urgently required.

中文翻译：

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外源 Aβ 种子诱导 Aβ 在血管而不是脑实质中沉积，与 Aβ 菌株特异性信息无关

关于脑实质或血管淀粉样蛋白 β 肽 (Aβ) 沉积的影响知之甚少。我们假设 Aβ 菌株特异性信息定义了 Aβ 是否沉积在脑实质或血管上。我们调查了 12 名具有不同严重程度的 Aβ 斑块和脑淀粉样血管病 (CAA) 的尸检患者，并使用阿尔茨海默病 (AD) 小鼠模型进行了播种研究，其中来自尸检患者的脑匀浆被脑内注射。根据主要病理特征，我们将尸检患者分为四组：AD、CAA、AD + CAA 和少 Aβ。注射一年后，在注射了人脑提取物的小鼠中，尸检人脑中 Aβ 的病理和生化特征并未保留。注射了所有四种人脑提取物的小鼠的 CAA 计数显着高于注射 PBS 的小鼠。有趣的是，在注射了来自较少 Aβ 组的人脑匀浆的小鼠中观察到了实质和血管 Aβ 沉积。Aβ和CAA播种活性与人脑提取物中的Aβ寡聚体比例呈显着正相关，Aβ较少组的人脑匀浆中的Aβ和CAA播种活性显着高于其他三组。这些结果表明，来自不同 Aβ 病理的外源性 Aβ 种子诱导 Aβ 在血管而非脑实质中沉积，而不受 Aβ 菌株特异性信息的影响，这可能是 CAA 是医源性传播病例中 Aβ 病理的主要特征的原因。