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      Gut microbiome alterations in Alzheimer’s disease

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          Abstract

          Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.

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          Most cited references34

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          Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota

          Alzheimer’s disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer’s disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aβ precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aβ amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aβ pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aβ levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.
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            MIND diet associated with reduced incidence of Alzheimer's disease.

            In a previous study, higher concordance to the MIND diet, a hybrid Mediterranean-Dietary Approaches to Stop Hypertension diet, was associated with slower cognitive decline. In this study we related these three dietary patterns to incident Alzheimer's disease (AD). We investigated the diet-AD relations in a prospective study of 923 participants, ages 58 to 98 years, followed on average 4.5 years. Diet was assessed by a semiquantitative food frequency questionnaire. In adjusted proportional hazards models, the second (hazards ratio or HR = 0.65, 95% confidence interval or CI 0.44, 0.98) and highest tertiles (HR = 0.47, 95% CI 0.26, 0.76) of MIND diet scores had lower rates of AD versus tertile 1, whereas only the third tertiles of the DASH (HR = 0.61, 95% CI 0.38, 0.97) and Mediterranean (HR = 0.46, 95% CI 0.26, 0.79) diets were associated with lower AD rates. High adherence to all three diets may reduce AD risk. Moderate adherence to the MIND diet may also decrease AD risk. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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              Diabetes mellitus and the risk of dementia: The Rotterdam Study.

              To determine the influence of type 2 diabetes mellitus on the risk of dementia and AD. Both dementia and diabetes are frequent disorders in elderly people. Prospective population-based cohort study among 6,370 elderly subjects. At baseline study participants were examined for presence of diabetes mellitus. Nondemented participants were followed up, on average, for 2.1 years. Incident dementia was diagnosed using a three-step screening and comprehensive diagnostic workup. To complete the follow-up, medical files were studied of persons who could not be reexamined. We estimated relative risks with proportional hazard regression, adjusting for age, sex, and possible confounders. During the follow-up, 126 patients became demented, of whom 89 had AD. Diabetes mellitus almost doubled the risk of dementia (relative risk [RR] 1.9 [1.3 to 2.8]) and AD (RR 1.9 [1.2 to 3.1]). Patients treated with insulin were at highest risk of dementia (RR 4.3 [1.7 to 10.5]). The diabetes attributable risk for dementia of 8.8% suggests that diabetes may have contributed to the clinical syndrome in a substantial proportion of all dementia patients.
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                Author and article information

                Contributors
                bbb@medicine.wisc.edu
                ferey@wisc.edu
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                19 October 2017
                19 October 2017
                2017
                : 7
                : 13537
                Affiliations
                [1 ]ISNI 0000 0001 2167 3675, GRID grid.14003.36, Wisconsin Alzheimer’s Disease Research Center, , University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue J5/1 Mezzanine, ; Madison, WI 53792 USA
                [2 ]ISNI 0000 0001 2167 3675, GRID grid.14003.36, Department of Bacteriology, , University of Wisconsin-Madison, 1550 Linden Drive, ; Madison, WI 53706 USA
                [3 ]ISNI 0000 0004 0420 6882, GRID grid.417123.2, Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, ; Madison, WI 53705 USA
                [4 ]ISNI 0000 0001 2167 3675, GRID grid.14003.36, Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health, WARF Building, 610 Walnut Street, 9th Floor, Suite 957, ; Madison, WI 53726 USA
                [5 ]ISNI 0000 0000 9919 9582, GRID grid.8761.8, Department of Psychiatry and Neurochemistry, , Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, ; Mölndal, Sweden
                [6 ]ISNI 000000009445082X, GRID grid.1649.a, Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, ; Mölndal, Sweden
                [7 ]ISNI 0000000121901201, GRID grid.83440.3b, Department of Molecular Neuroscience, , University College London Institute of Neurology, Queen Square, ; London, United Kingdom
                [8 ]ISNI 0000000121901201, GRID grid.83440.3b, UK Dementia Research Institute at University College London, ; London, United Kingdom
                Author information
                http://orcid.org/0000-0002-2334-1495
                http://orcid.org/0000-0003-1481-7065
                Article
                13601
                10.1038/s41598-017-13601-y
                5648830
                29051531
                2ebd423f-0b62-4d3b-bd70-3b4a73c4067c
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 21 June 2017
                : 27 September 2017
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