Age-related disease may be mediated by low levels of chronic inflammation ("inflammaging"). Recent work suggests that gut microbes may contribute to inflammation via degradation of the intestinal barrier. While aging and age-related diseases including Alzheimer's disease (AD) are linked to altered microbiome composition and higher levels of gut microbial components in systemic circulation, the role of intestinal inflammation and permeability per se remains unclear. To test whether greater gut inflammation is associated with older age and AD pathology, we assessed fecal samples from older adults to measure calprotectin, an established marker of intestinal inflammation which is elevated in diseases of gut barrier integrity. Here we found that calprotectin levels are higher with age, and that higher calprotectin was associated with greater amyloid burden among participants with an amyloid-confirmed AD dementia diagnosis. Calprotectin was also associated with cerebrospinal fluid markers of AD pathology and axonal degeneration, as well as with lower verbal memory function among cognitively unimpaired participants. Together, these findings suggest that intestinal inflammation may play a role in pathology development, and that it may exacerbate the progression toward AD.

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与年龄和阿尔茨海默病病理学相关的肠道炎症

与年龄相关的疾病可能由低水平的慢性炎症（“炎症”）介导。最近的研究表明，肠道微生物可能通过肠道屏障的降解导致炎症。虽然包括阿尔茨海默病 (AD) 在内的衰老和与年龄相关的疾病与体循环中微生物组组成的改变和更高水平的肠道微生物成分有关，但肠道炎症和通透性本身的作用仍不清楚。为了测试更大的肠道炎症是否与老年人和 AD 病理学相关，我们评估了老年人的粪便样本以测量钙卫蛋白，这是一种肠道炎症的既定标志物，在肠道屏障完整性疾病中升高。在这里我们发现钙卫蛋白水平随着年龄的增长而升高，在经淀粉样蛋白确认的 AD 痴呆诊断的参与者中，较高的钙卫蛋白与较大的淀粉样蛋白负担相关。钙卫蛋白还与 AD 病理学和轴索变性的脑脊液标志物以及认知未受损参与者的语言记忆功能降低有关。总之，这些发现表明肠道炎症可能在病理学发展中发挥作用，并且它可能会加剧向 AD 的进展。