Genotype and microbiome shape immunity in a sex-specific manner in mouse models of Alzheimer's disease

Abstract

Copyright and License

© 2025 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Acknowledgement

We thank the Mazmanian laboratory for helpful suggestions on this work and Catherine Oikonomou for assistance with manuscript editing. We thank the Caltech Flow Cytometry and Cell Sorting Facility for flow cytometry services and assistance. J.W.B. was supported by the Research and Outreach Fellowship awarded by the Caltech Biology and Biological Engineering Division. This project was enabled in part by the Alzheimer's Gut Microbiome Project (AGMP), supported by the National Institute on Aging grants: 1U19AG063744 and 3U19AG063744-04S1, awarded to R.K.-D., R.K., and S.K.M., in partnership with multiple academic institutions. As such, the investigators within the AGMP not listed in this publication's authors' list provided analysis-ready data, but did not participate in designing the study, conducting the analyses or writing of this manuscript. A listing of AGMP Investigators can be found at https://alzheimergut.org/meet-the-team/. The NIA supported the Alzheimer's Disease Metabolomics Consortium which is a part of NIA's national initiatives AMP-AD and M2OVE-AD (R01 AG046171, RF1 AG059093, RF1 AG058942, RF1 AG051550, 3U01 AG061359, 3U01 AG024904-09S4). Additional funding for this project came from the Heritage Medical Research Institute (HMRI-15-09-01) to S.K.M.

Data Availability

Data will be made available on request.

Conflict of Interest

R.K.-D. is an inventor on a series of patents on use of metabolomics for the diagnosis and treatment of CNS diseases and holds equity in Metabolon Inc., Chymia LLC and PsyProtix. R.K. is a scientific advisory board member, and consultant for BiomeSense, Inc., has equity, and receives income. He is a scientific advisory board member and has equity in GenCirq. He is a consultant for DayTwo, and receives income. He has equity in and acts as a consultant for Cybele. He is a co-founder of Biota, Inc., and has equity. He is a cofounder of Micronoma, and has equity and is a scientific advisory board member. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. S.K.M. is a co-founder of Axial Therapeutics and Nuanced Health, and declares no competing interests with the current studies. The remaining authors have no interests to declare.

Contributions

John W. Bostick: Writing – original draft, Methodology, Investigation. T. Jaymie Connerly: Methodology, Investigation. Taren Thron: Investigation. Brittany D. Needham: Methodology. Matheus de Castro Fonseca: Investigation. Rima Kaddurah-Daouk: Writing – review & editing, Funding acquisition, Conceptualization. Rob Knight: Writing – review & editing, Funding acquisition. Sarkis K. Mazmanian: Writing – review & editing, Supervision, Funding acquisition, Conceptualization.

Supplemental Material

Supplementary Data 1 (PDF)

Supplementary Data 2 (PDF)