{Reference Type}: Journal Article
{Title}: Sex-specific associations between AD genotype and the microbiome of human amyloid beta knock-in (hAβ-KI) mice.
{Author}: Dunham SJB;Avelar-Barragan J;Rothman JA;Adams ED;Faraci G;Forner S;Kawauchi S;Tenner AJ;Green KN;LaFerla FM;MacGregor GR;Mapstone M;Whiteson KL;
{Journal}: Alzheimers Dement
{Volume}: 20
{Issue}: 7
{Year}: 2024 07 4
{Factor}: 16.655
{DOI}: 10.1002/alz.13794
{Abstract}: 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.<BR>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).<BR>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 distinguishable from 3xTg-AD animals (81% accuracy by random forest modeling), with separation primarily driven by Romboutsia ilealis and Turicibacter species. Microbiomes were highly cage specific, with cage assignment accounting for more than 40% of the PERMANOVA variance between the groups.<BR>These findings highlight a sex-dependent variation in the microbiomes of hAβ-KI mice and underscore the importance of considering the microbiome when designing studies that use murine models for AD.<BR>Microbial diversity and the abundance of several species differed in human amyloid beta knock-in (hAβ-KI) females but not males. Correlations to Alzheimer's disease (AD) genotype were stronger for the microbiome than the metabolome. Microbiomes from hAβ-KI mice were distinct from 3xTg-AD mice. Cage effects accounted for most of the variance in the microbiome and metabolome.