Gut inflammation associated with age and Alzheimer’s disease pathology
Gut inflammation associated with age and Alzheimer’s disease pathology
Abstract 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. SummaryIntestinal inflammation is correlated with older age, Alzheimer’s disease (AD) dementia, and greater amyloid burden in participants with AD.
Zarbock Katie R.、Davenport-Sis Nancy J.、Hoeft Ana、Wild Norbert、Zetterberg Henrik、Deming Yuetiva、Kollmorgen Gwendlyn、Hanslik Kendra L.、Rey Federico E.、Johnson Sterling C.、Betthauser Tobey J.、Vogt Nicholas M.、Suridjan Ivonne、Blennow Kaj、Bendlin Barbara B.、Sun Yi、Ulland Tyler K.、Chin Nathaniel、Kerby Robert L.、Harding Sandra J.、Asthana Sanjay、Heston Margo B.
Department of Bacteriology, University of Wisconsin-MadisonWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public HealthWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public HealthRoche Diagnostics GmbHDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg||Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital||Department of Neurodegenerative Disease, UCL Institute of Neurology||UK Dementia Research Institute at UCL||Hong Kong Center for Neurodegenerative DiseasesWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public Health||Wisconsin Alzheimer?ˉs Institute, University of Wisconsin School of Medicine and Public HealthRoche Diagnostics GmbHDepartment of Pathology and Laboratory Medicine, University of Wisconsin-MadisonDepartment of Bacteriology, University of Wisconsin-MadisonWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public Health||Wisconsin Alzheimer?ˉs Institute, University of Wisconsin School of Medicine and Public HealthWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public HealthWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public HealthRoche Diagnostics International LtdDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg||Clinical Neurochemistry Laboratory, Sahlgrenska University HospitalWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public Health||Wisconsin Alzheimer?ˉs Institute, University of Wisconsin School of Medicine and Public HealthDepartment of Bacteriology, University of Wisconsin-MadisonDepartment of Pathology and Laboratory Medicine, University of Wisconsin-MadisonWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public HealthDepartment of Bacteriology, University of Wisconsin-MadisonWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public HealthWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public HealthWisconsin Alzheimer?ˉs Disease Research Center, University of Wisconsin School of Medicine and Public Health
神经病学、精神病学基础医学微生物学
Zarbock Katie R.,Davenport-Sis Nancy J.,Hoeft Ana,Wild Norbert,Zetterberg Henrik,Deming Yuetiva,Kollmorgen Gwendlyn,Hanslik Kendra L.,Rey Federico E.,Johnson Sterling C.,Betthauser Tobey J.,Vogt Nicholas M.,Suridjan Ivonne,Blennow Kaj,Bendlin Barbara B.,Sun Yi,Ulland Tyler K.,Chin Nathaniel,Kerby Robert L.,Harding Sandra J.,Asthana Sanjay,Heston Margo B..Gut inflammation associated with age and Alzheimer’s disease pathology[EB/OL].(2025-03-28)[2025-06-03].https://www.medrxiv.org/content/10.1101/2022.09.21.22280179.点此复制
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