
==== Front
medRxiv
MEDRXIV
medRxiv
Cold Spring Harbor Laboratory

10.1101/2024.09.04.24313004
preprint
1
Article
Gut microbiome compositional and functional features associate with Alzheimer’s disease pathology
Kang Jea Woo
Khatib Lora A.
Heston Margo B. http://orcid.org/0000-0002-0980-2275

Dilmore Amanda H.
Labus Jennifer S.
Deming Yuetiva http://orcid.org/0000-0001-7512-5703

Schimmel Leyla
Blach Colette
McDonald Daniel
Gonzalez Antonio
Bryant MacKenzie
Sanders Karenina
Schwartz Lara
Ulland Tyler K.
Johnson Sterling C.
Asthana Sanjay
Carlsson Cynthia M.
Chin Nathaniel A.
Blennow Kaj
Zetterberg Henrik
Rey Federico E.
Alzheimer Gut Microbiome Project Consortium
Kaddurah-Daouk Rima
Knight Rob
Bendlin Barbara B.
05 9 2024
2024.09.04.24313004https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://medrxiv.org/lookup/doi/10.1101/2024.09.04.24313004
nihpp-2024.09.04.24313004.pdf
Abstract

BACKGROUND

The gut microbiome is a potentially modifiable factor in Alzheimer’s disease (AD); however, understanding of its composition and function regarding AD pathology is limited.

METHODS

Shallow-shotgun metagenomic data was used to analyze fecal microbiome from participants enrolled in the Wisconsin Microbiome in Alzheimer’s Risk Study, leveraging clinical data and cerebrospinal fluid (CSF) biomarkers. Differential abundance and ordinary least squares regression analyses were performed to find differentially abundant gut microbiome features and their associations with CSF biomarkers of AD and related pathologies.

RESULTS

Gut microbiome composition and function differed between people with AD and cognitively unimpaired individuals. The compositional difference was replicated in an independent cohort. Differentially abundant gut microbiome features were associated with CSF biomarkers of AD and related pathologies.

DISCUSSION

These findings enhance our understanding of alterations in gut microbial composition and function in AD, and suggest that gut microbes and their pathways are linked to AD pathology.
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