Evidence map›Paper›PMID 42113045›Full record

ArticleCellular and molecular neurobiology2026

Fecal miRNome and Proteome Profiling Uncovers Stage-Specific Biomarkers of Alzheimer's Disease in 3×Tg-AD Mice.

Roberta Vitali, Barbara Tanno, Arianna Casciati, Francesca Palone, Luisa Pieroni, Marta Morotti, Massimo Santoro, Emiliano Fratini, Simonetta Pazzaglia, Maria Vittoria Podda and 1 more

Abstract read
In one paragraph

Article in Cellular and molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Roberta Vitali *Biotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy.ORCID https://orcid.org/0000-0003-4203-0163
Barbara Tanno *Biotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy.ORCID https://orcid.org/0000-0001-6098-699X
Arianna CasciatiBiotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy.ORCID https://orcid.org/0000-0003-2487-3060
Francesca PaloneBiotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy.ORCID https://orcid.org/0000-0001-7700-9466
Luisa PieroniDepartmental Faculty of Medicine, UniCamillus-Saint Camillus International University of Health and Medical Sciences, 00131, Rome, Italy.ORCID https://orcid.org/0000-0001-7141-1817
Marta MorottiFondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.ORCID https://orcid.org/0000-0003-1878-0159
Massimo SantoroBiotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy.ORCID https://orcid.org/0000-0002-3037-2775
Emiliano FratiniBiotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy.ORCID https://orcid.org/0000-0003-2522-1718
Simonetta PazzagliaBiotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy.ORCID https://orcid.org/0000-0003-2078-4466
Maria Vittoria PoddaFondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. mariavittoria.podda@unicatt.it.ORCID https://orcid.org/0000-0002-2779-8417
Mariateresa MancusoBiotechnologies Division, National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), 00123, Rome, Italy. mariateresa.mancuso@enea.it.ORCID https://orcid.org/0000-0002-0912-9287

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reliable, minimally invasive biomarkers for Alzheimer's disease (AD) remain a critical unmet need. Considering mounting evidence for gut-brain interactions in AD, we explored whether fecal samples contain host-derived molecular signals that reflect disease-related changes and could serve as accessible biomarkers. Fecal small RNA sequencing and quantitative proteomics were performed in symptomatic 15-month-old 3×Tg-AD mice and controls. Pathway and network analyses identified key dysregulated molecules. Selected miRNAs and proteins were validated by qPCR or Western blotting in independent pre-symptomatic, early symptomatic, and severe cohorts. To assess whether fecal signals mirrored tissue alterations, colon samples were analyzed for tight-junction proteins, inflammatory markers, epigenetic regulation, and expression of selected miRNAs and proteins. Multi-omics identified 31 miRNAs and 81 proteins modulated in AD fecal sample, revealing a distinct AD-associated fecal signature involving pathways linked to neuroinflammation, synaptic dysfunction, vascular imbalance, and metabolism. Several miRNAs- including miR-322-5p, miR-194-1 and miR-223-3p were significantly altered and validated across disease stages (3-,7-,15-old months mice, respectively). Notably, miR-146b-5p expression is inversely correlated with AD severity, exhibiting a stepwise decline from asymptomatic individuals to those with mild and severe stages. IgKappa and Ela3B emerged as the strongest protein candidates, showing opposite and progressive modulation. Notably, IgKappa and miR-146b showed the most consistent trajectories. Colon analyses uncovered reduced Claudin-7, strong IgKappa upregulation driven by enhancer hypomethylation, and partial overlap between fecal and tissue miRNA profiles, indicating that fecal signals reflect subtle epithelial and immune perturbations associated with AD. Multi-omics at severe stage and a stage specific validation support fecal miRNAs and proteins as promising, host-derived biomarkers for AD. Fecal profiling offers a practical, repeatable, and low-cost approach with translational potential for early detection and longitudinal monitoring in neurodegeneration.

Indexed as

Alzheimer DiseaseFecesMicroRNAsProteomeAnimalsBiomarkersGene Expression ProfilingMaleMiceMice, TransgenicMultiomicsProteomicsBiomarkersMicroRNAsProteomeEarly diagnosisElastase3BGut-brain axisIgKappaIntestinal barrier dysfunctionmiR-146b-5pMultiomicsStool

Identifiers

PMID42113045
PMCPMC13332079

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.