biostudies-literatureDunham SJBNIA NIH HHSHewitt Foundation for Biomedical ResearchNCI NIH HHSNational Cancer Institute of the National Institutes of HealthNational Institute on Aging4935-4950https://www.ebi.ac.uk/biostudies/studies/S-EPMC11247698biostudies-literatureUnknown20(7)<h4>Introduction</h4>Emerging evidence links changes in the gut microbiome to late-onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.<h4>Methods</h4>We used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock-in (hAβ-KI) murine model for LOAD compared to both wild-type (WT) mice and a model for early-onset AD (3xTg-AD).<h4>Results</h4>Eighteen-month female (but not male) hAβ-KI 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. hAβ-KI mice microbiomes were diAlzheimer's & dementia : the journal of the Alzheimer's AssociationSex-specific associations between AD genotype and the microbiome of human amyloid beta knock-in (hAβ-KI) mice.PMC11247698T32 AG00096‐38P30 CA062203T32 AG000096T32 AG00096-38U54 AG054349P30CA062203Avelar-Barragan JMapstone MRothman JAKawauchi SForner SDunham SJBFaraci GMacGregor GRAdams EDWhiteson KLGreen KNTenner AJLaFerla FMfalseSex-specific associations between AD genotype and the microbiome of human amyloid beta knock-in (hAβ-KI) mice.<h4>Introduction</h4>Emerging evidence links changes in the gut microbiome to late-onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.<h4>Methods</h4>We used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock-in (hAβ-KI) murine model for LOAD compared to both wild-type (WT) mice and a model for early-onset AD (3xTg-AD).<h4>Results</h4>Eighteen-month female (but not male) hAβ-KI 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. hAβ-KI mice microbiomes were di2024-01-01T00:00:00Z2024 Jul2026-06-02T22:24:07.581Z2024-12-04T03:17:08.105ZS-EPMC112476983857286510.1002/alz.13794