Although amyloid-β42 (Aβ42) has been used as one of the core biomarkers for Alzheimer's disease (AD) diagnosis, the dynamic changes of its different forms in the brain, blood, and even intestines and its correlation with the progression of AD disease remain obscure. Herein, we screened Aβ42-specific preferred antibody pairs 1F12/1F12 and 1F12/2C6 to accurately detect Aβ42 types using sandwich ELISA, including total Aβ42, Aβ42 oligomers (Aβ42Os), and Aβ42 monomers (Aβ42Ms). The levels of Aβ42 species in the brain, blood, and intestines of different aged APP/PS1 mice were quantified to study their correlation with AD progression. Total Aβ42 levels in the blood were not correlated with AD progression, but Aβ42Ms level in the blood of 9-month-old APP/PS1 mice was significantly reduced, and Aβ42Os level in the brain was significantly elevated compared to 3-month-old APP/PS1, demonstrating that the levels of Aβ42Ms and Aβ42Os in the blood and brain were correlated with AD progression. Interestingly, in 9-month-old APP/PS1 mice, the level of Aβ42 in the intestine was higher than that in 3-month-old APP/PS1 mice, indicating that the increased level of Aβ42 in the gastrointestinal organs may also be related to the progression of AD. Meanwhile, changes in the gut microbiota composition of APP/PS1 mice with age were also observed. Therefore, the increase in Aβ derived from intestinal tissues and changes in microbiome composition can be used as a potential early diagnosis tool for AD, and further used as an indicator of drug intervention to reduce brain amyloid.

中文翻译：

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APP/PS1 小鼠大脑和外周淀粉样蛋白-β42 水平的动态变化及其对阿尔茨海默病的意义。

尽管淀粉样蛋白-β42 (Aβ42) 已被用作阿尔茨海默病 (AD) 诊断的核心生物标志物之一，但其不同形式在大脑、血液甚至肠道中的动态变化及其与 AD 疾病进展的相关性仍然存在朦胧。在此，我们筛选了 Aβ42 特异性优选抗体对 1F12/1F12 和 1F12/2C6，以使用夹心 ELISA 准确检测 Aβ42 类型，包括总 Aβ42、Aβ42 寡聚体 (Aβ42Os) 和 Aβ42 单体 (Aβ42Ms)。量化不同年龄 APP/PS1 小鼠大脑、血液和肠道中 Aβ42 的水平，以研究它们与 AD 进展的相关性。血液中的总 Aβ42 水平与 AD 进展无关，但 9 个月大的 APP/PS1 小鼠血液中的 Aβ42Ms 水平显着降低，与 3 个月大的 APP/PS1 相比，大脑中的 Aβ42Os 水平显着升高，表明血液和大脑中的 Aβ42Ms 和 Aβ42Os 水平与 AD 进展相关。有趣的是，9月龄APP/PS1小鼠肠道Aβ42水平高于3月龄APP/PS1小鼠，提示胃肠道Aβ42水平升高也可能与到 AD 的进展。同时，还观察到 APP/PS1 小鼠肠道菌群组成随年龄的变化。因此，肠道组织来源的Aβ增加和微​​生物组组成的变化可作为AD潜在的早期诊断工具，进一步作为药物干预减少脑淀粉样蛋白的指标。证明血液和大脑中 Aβ42Ms 和 Aβ42Os 的水平与 AD 进展相关。有趣的是，9月龄APP/PS1小鼠肠道Aβ42水平高于3月龄APP/PS1小鼠，提示胃肠道Aβ42水平升高也可能与到 AD 的进展。同时，还观察到 APP/PS1 小鼠肠道菌群组成随年龄的变化。因此，肠道组织来源的Aβ增加和微​​生物组组成的变化可作为AD潜在的早期诊断工具，进一步作为药物干预减少脑淀粉样蛋白的指标。证明血液和大脑中 Aβ42Ms 和 Aβ42Os 的水平与 AD 进展相关。有趣的是，9月龄APP/PS1小鼠肠道Aβ42水平高于3月龄APP/PS1小鼠，提示胃肠道Aβ42水平升高也可能与到 AD 的进展。同时，还观察到 APP/PS1 小鼠肠道菌群组成随年龄的变化。因此，肠道组织来源的Aβ增加和微​​生物组组成的变化可作为AD潜在的早期诊断工具，进一步作为药物干预减少脑淀粉样蛋白的指标。肠道内 Aβ42 水平高于 3 月龄 APP/PS1 小鼠，提示胃肠道内 Aβ42 水平升高也可能与 AD 的进展有关。同时，还观察到 APP/PS1 小鼠肠道菌群组成随年龄的变化。因此，肠道组织来源的Aβ增加和微​​生物组组成的变化可作为AD潜在的早期诊断工具，进一步作为药物干预减少脑淀粉样蛋白的指标。肠道内 Aβ42 水平高于 3 月龄 APP/PS1 小鼠，提示胃肠道内 Aβ42 水平升高也可能与 AD 的进展有关。同时，还观察到 APP/PS1 小鼠肠道菌群组成随年龄的变化。因此，肠道组织来源的Aβ增加和微​​生物组组成的变化可作为AD潜在的早期诊断工具，进一步作为药物干预减少脑淀粉样蛋白的指标。