Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Sci Rep. 2023 Nov 14;13(1):18924. doi: 10.1038/s41598-023-45929-z.
Age-related disease may be mediated by low levels of chronic inflammation ("inflammaging"). Recent work suggests that gut microbes can 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 remains unclear. To investigate whether greater gut inflammation is associated with advanced 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. Multiple regression with maximum likelihood estimation and Satorra-Bentler corrections were used to test relationships between fecal calprotectin and clinical diagnosis, participant age, cerebrospinal fluid biomarkers of AD pathology, amyloid burden measured using C-Pittsburgh compound B positron emission tomography (PiB PET) imaging, and performance on cognitive tests measuring executive function and verbal learning and recall. Calprotectin levels were elevated in advanced age and were higher in participants diagnosed with amyloid-confirmed AD dementia. Additionally, among individuals with AD dementia, higher calprotectin was associated with greater amyloid burden as measured with PiB PET. Exploratory analyses indicated that calprotectin levels were also associated with cerebrospinal fluid markers of AD, and with lower verbal memory function even among cognitively unimpaired participants. Taken together, these findings suggest that intestinal inflammation is linked with brain pathology even in the earliest disease stages. Moreover, intestinal inflammation may exacerbate the progression toward AD.
年龄相关疾病可能由慢性低度炎症（“炎症老化”）介导。最近的研究表明，肠道微生物可能通过降解肠道屏障而导致炎症。虽然衰老和阿尔茨海默病（AD）等与肠道微生物群落组成改变以及全身性循环中更高水平的肠道微生物成分有关，但肠道炎症的作用仍不清楚。为了研究肠道炎症是否与年龄增长和 AD 病理有关，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。使用最大似然估计和 Satorra-Bentler 校正的多元回归来测试粪便钙卫蛋白与临床诊断、参与者年龄、AD 病理的脑脊液生物标志物、使用 C-Pittsburgh 化合物 B 正电子发射断层扫描 (PiB PET) 测量的淀粉样蛋白负荷以及用于测量执行功能和语言学习和记忆的认知测试之间的关系。钙卫蛋白水平在高龄时升高，在被诊断为淀粉样蛋白确诊 AD 痴呆的参与者中更高。此外，在 AD 痴呆患者中，钙卫蛋白水平越高，PiB PET 测量的淀粉样蛋白负荷越大。探索性分析表明，钙卫蛋白水平也与 AD 的脑脊液标志物相关，甚至在认知未受损的参与者中，钙卫蛋白水平也与较低的语言记忆功能相关。综上所述，这些发现表明，即使在疾病的早期阶段，肠道炎症也与大脑病理有关。此外，肠道炎症可能会加重向 AD 的进展。
