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Microbiome functional gene pathways are indicative of cognitive performance in older adults at risk for Alzheimer's disease

Zeamer, Abigail L
Lai, YuShuan
Loew, Ethan
Sanborn, Victoria
Tracy, Matthew
Jo, Cynthia
Ferdinand, Danielle
Ward, Doyle V
Bhattarai, Shakti K
Drake, Johnathan
... show 3 more
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Abstract

Disturbances in the gut microbiome are increasingly correlated with neurodegenerative disorders, including Alzheimer's disease. Multiple lines of emerging evidence are consistent with the microbiome's involvement in disease pathology in AD by triggering or potentiating systemic and neuroinflammation, thereby influencing disease pathology through the "microbiota-gut-brain axis." Currently, the copathologies contributing to cognitive decline and symptomatic progression in AD remain unknown and understudied. Changes in the gut microbiome composition may offer clues to potential systemic physiologic and neuropathologic changes that contribute to cognitive decline. Here, we recruited a cohort of 260 older adults (aged 60 y or older) living in the community and followed them over time, tracking objective measures of cognition, clinical information, and gut microbiome samples. Subjects were classified as healthy controls, exhibiting mild cognitive impairment, or having dementia based on clinical assessments. Using metagenomic sequencing and gene pathway analyses, we found that certain microbial-encoded metabolic pathways correlated with worse cognitive performance. Specifically, genes involved in the urea cycle, polyamine synthesis, or the metabolism of methionine and cysteine predicted worse cognitive performance. Our study suggests that the gut microbiome composition may be linked to cognitive impairment along the AD continuum and points to microbial metabolic pathways that may potentiate disease.

Source

Zeamer AL, Lai Y, Loew E, Sanborn V, Tracy M, Jo C, Ferdinand D, Ward DV, Bhattarai SK, Drake J, McCormick BA, Bucci V, Haran JP. Microbiome functional gene pathways are indicative of cognitive performance in older adults at risk for Alzheimer's disease. Gut Microbes. 2026 Dec 31;18(1):2676162. doi: 10.1080/19490976.2026.2676162. Epub 2026 May 24. PMID: 42178714; PMCID: PMC13203045.

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DOI
10.1080/19490976.2026.2676162
PubMed ID
42178714
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This article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2025.03.06.641911

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© 2026 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.