Alzheimer's disease (AD) is characterized by the presence of proteinaceous brain deposits, brain atrophy, vascular dysfunction, and chronic inflammation. Along with cerebral inflammation, peripheral inflammation is also evident in many AD patients. Bradykinin, a proinflammatory plasma peptide, is also linked to AD pathology. For example, bradykinin infusion into the hippocampus causes learning and memory deficits in rats, and blockade of the bradykinin receptor lessens cognitive impairment in AD mouse models. Even though it has been hypothesized that plasma bradykinin could contribute to inflammation in AD, the level of plasma bradykinin and its association with beta-amyloid (Aβ) pathology in AD patients had not been explored. Here, we assessed plasma bradykinin levels in AD patients and age-matched non-demented (ND) control individuals. We found significantly elevated plasma bradykinin levels in AD patients compared to ND subjects. Additionally, changes in plasma bradykinin levels were more profound in many AD patients with severe cognitive impairment, suggesting that peripheral bradykinin could play a role in dementia most likely via inflammation. Bradykinin levels in the cerebrospinal fluid (CSF) were reduced in AD patients and exhibited an inverse correlation with the CSF Aβ40/Aβ42 ratio. We also report that bradykinin interacts with the fibrillar form of Aβ and co-localizes with Aβ plaques in the post-mortem human AD brain. These findings connect the peripheral inflammatory pathway to cerebral abnormalities and identify a novel mechanism of inflammatory pathology in AD.

中文翻译：

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血浆缓激肽水平升高与阿尔茨海默病患者的认知障碍有关。

阿尔茨海默病（AD）的特征是存在蛋白质脑沉积、脑萎缩、血管功能障碍和慢性炎症。除了脑部炎症外，许多 AD 患者的周围炎症也很明显。缓激肽是一种促炎血浆肽，也与 AD 病理有关。例如，将缓激肽注入海马会导致大鼠的学习和记忆缺陷，而阻断缓激肽受体可减轻 AD 小鼠模型的认知障碍。尽管有人假设血浆缓激肽可能导致 AD 炎症，但血浆缓激肽水平及其与 AD 患者 β-淀粉样蛋白 (Aβ) 病理学的关系尚未得到探索。在这里，我们评估了 AD 患者和年龄匹配的非痴呆 (ND) 对照个体的血浆缓激肽水平。我们发现 AD 患者的血浆缓激肽水平显着高于 ND 受试者。此外，许多患有严重认知障碍的 AD 患者血浆缓激肽水平的变化更为严重，这表明外周缓激肽很可能通过炎症在痴呆中发挥作用。AD 患者脑脊液 (CSF) 中的缓激肽水平降低，并与 CSF Aβ40/Aβ42 比率呈负相关。我们还报告说，缓激肽与 Aβ 纤维状形式相互作用，并与死后人类 AD 大脑中的 Aβ 斑块共定位。这些发现将外周炎症通路与大脑异常联系起来，并确定了 AD 炎症病理学的新机制。