{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:51:16Z","timestamp":1781715076026,"version":"3.54.5"},"reference-count":58,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T00:00:00Z","timestamp":1712188800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U54 AG054349"],"award-info":[{"award-number":["U54 AG054349"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32 AG00096\u201038"],"award-info":[{"award-number":["T32 AG00096\u201038"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>Emerging evidence links changes in the gut microbiome to late\u2010onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock\u2010in (hA\u03b2\u2010KI) murine model for LOAD compared to both wild\u2010type (WT) mice and a model for early\u2010onset AD (3xTg\u2010AD).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Eighteen\u2010month female (but not male) hA\u03b2\u2010KI microbiomes were distinct from WT microbiomes, with AD genotype accounting for 18% of the variance by permutational multivariate analysis of variance (PERMANOVA). Metabolomic diversity differences were observed in females, however no individual metabolites were differentially abundant. hA\u03b2\u2010KI mice microbiomes were distinguishable from 3xTg\u2010AD animals (81% accuracy by random forest modeling), with separation primarily driven by <jats:italic>Romboutsia ilealis<\/jats:italic> and <jats:italic>Turicibacter<\/jats:italic> species. Microbiomes were highly cage specific, with cage assignment accounting for more than 40% of the PERMANOVA variance between the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>These findings highlight a sex\u2010dependent variation in the microbiomes of hA\u03b2\u2010KI mice and underscore the importance of considering the microbiome when designing studies that use murine models for AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Microbial diversity and the\u00a0abundance of several species differed in human amyloid beta knock\u2010in (hA\u03b2\u2010KI) females but not males.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Correlations to Alzheimer's disease (AD) genotype were stronger for the microbiome than the metabolome.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Microbiomes from hA\u03b2\u2010KI mice were distinct from 3xTg\u2010AD mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cage effects accounted for most of the variance in the microbiome and metabolome.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13794","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T08:05:52Z","timestamp":1712217952000},"page":"4935-4950","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Sex\u2010specific associations between AD genotype and the microbiome of human amyloid beta knock\u2010in (hA\u03b2\u2010KI) mice"],"prefix":"10.1002","volume":"20","author":[{"given":"Sage J. 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