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Record W4413836685 · doi:10.1016/j.celrep.2025.116109

Amyloid-β-driven Alzheimer’s disease reshapes the colonic immune system in mice

2025· article· en· W4413836685 on OpenAlexafffund
Priya Makhijani, Taylor R. Valentino, Max Manwaring-Mueller, Rohini Emani, Wei‐Chieh Mu, Carlos Galicia Aguirre, Christopher Tan, Anand Rane, Kenneth A. Wilson, A Kifle, Nan Chen, Huixun Du, Fei Wu, Jenny Hong Yu Ng, Benjamin D Ambrose, Prasanna Vadhana Ashok Kumaar, Saad Khan, Shawn Winer, Chao Wang, Arthur Mortha, David Furman, Birgit Schilling, Lisa Ellerby, Olga Lucía Agudelo Rojas, Julie K. Andersen, Daniel A. Winer

Bibliographic record

VenueCell Reports · 2025
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsToronto Rehabilitation InstituteSunnybrook Health Science CentreMount Sinai HospitalOntario Brain InstituteUniversity of TorontoUniversity Health Network
FundersNational Institute on AgingCanadian Institutes of Health ResearchNational Institute of Diabetes and Digestive and Kidney DiseasesKrembil FoundationNational Institutes of HealthBuck Institute for Research on AgingFoundation for the National Institutes of Health
KeywordsImmune systemDiseaseAmyloid (mycology)Alzheimer's diseaseAmyloid βNeuroscienceMedicineImmunologyBiologyPathology

Abstract

fetched live from OpenAlex

The "gut-brain axis" is an emerging target in Alzheimer's disease (AD), although its immunological features remain poorly understood. Using single-cell RNA sequencing, coupled to extensive spectral-tuning flow cytometry validation of the colon immune compartment in the 5XFAD amyloid-β mouse model, we found several AD-associated changes including in B/plasma cell activity. Notably, levels of CXCR4 + antibody-secreting cells are reduced in 5XFAD colons. This change corresponds with accumulating CXCR4 + B cells and gut-specific IgA + cells in the brain and dura mater, respectively. Consistently, a chemokine ligand for CXCR4, CXCL12, is expressed at higher levels in the 5XFAD brain and in in silico -analyzed human AD brain studies, supporting altered neuroimmune trafficking. An inulin prebiotic fiber diet could expand gut IgA + cells, rescue peripheral T reg levels, reduce dysbiosis, improve serum microbial metabolite levels, and attenuate overall AD-associated frailty. Our study reveals key aspects of the gut-brain axis and highlights potential targets against AD.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.297
Teacher spread0.278 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations5
Published2025
Admission routes2
Has abstractyes

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