Multi-regional transcriptomic analysis reveals early nociceptive and neuroinflammatory alterations in APP/PS1 mice.

Overview

1. Department of Anesthesiology, Rutgers, the State University of New Jersey, Newark, NJ, United States
2. Department of Pharmaceutical Sciences, School of Pharmacy, University at Buffalo, The State University of New York, Buffalo, NY, United States
3. Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, United States

Abstract

Background: BackgroundAlzheimer's disease (AD) is characterized by progressive cognitive decline and neuropsychiatric symptoms, including chronic neuropathic pain. However, the molecular mechanisms linking pain sensitivity to early AD pathology remain poorly understood.

Methods: In the present study, 4- to 5-month-old APP/PS1 mice were used to identify molecular signatures of the early pathological stage. Transcriptomic analysis, quantitative real-time RT-PCR (qRT-PCR), immunoblot, and ELISA analyses were performed to assess region-specific gene expression, neuroinflammation, and synaptic protein levels in pain-related regions.

Results: Although memory behaviors remained unchanged in 4–5-month-old APP/PS1 mice, these mice showed an increase in whole-brain Aβ plaque burden. Transcriptomic analysis and qRT-PCR revealed distinct region-specific gene expression changes. Plin4 was downregulated in the DRG, spinal cord, thalamus, and hippocampus of APP/PS1 mice. Rps3a3 and Prnp were significantly upregulated in both the spinal cord and thalamus, whereas Hif3a and Serpina3f were significantly upregulated in the thalamus and hippocampus. These gene alterations were closely involved in inflammatory responses and synaptic plasticity. Immunoblot and ELISA analyses in these pain-related regions demonstrated increased TNF-α and IL-1β levels, as well as reduced expression of synaptic proteins, indicating enhanced neuroinflammation and synaptic loss in the early stages of APP/PS1 mice.

Conclusion: These findings support the presence of neuroinflammation and synaptic dysfunction in pain-processing circuits as early molecular events in APP/PS1 mice, suggesting that nociceptive alterations may represent an early feature of the pathological stage of AD.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

• geo:GSE33000, at NCBI GEO; found in the text, “Cross-species validation of candidate genes in…”
• zenodo:17517310, at Zenodo; found in “Data availability statement”

Data availability statement

The datasets presented in this study can be found in online repositories (https://doi.org/10.5281/zenodo.17517310). The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 10 authors, 5 keywords, 13 MeSH terms, 1 funder, 74 references, 2 RRIDs.

Cite

This paper

Sheng, Z., Xu, F., Yan, Y., Chen, L., Dou, B., Liu, N., Zhou, S., Zhu, X., Tao, Y.-X., & Xu, Y. (2026). Multi-regional transcriptomic analysis reveals early nociceptive and neuroinflammatory alterations in APP/PS1 mice. Frontiers in immunology, 17, 1937738. https://doi.org/10.3389/fimmu.2026.1937738

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1038/s41419-026-08791-1

The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease.

Journal: Cell death & disease

In common: NCBI GEO GSE33000, Alzheimer's / dementia, genetics / omics, mouse, 1 other category

[2] doi:10.1038/s41467-026-75895-9

Distinct Filament Conformation for Receptor-Bound Amyloid-β from Alzheimer's Disease Brain.

Journal: Nature communications

In common: Alzheimer's / dementia, cellular / molecular, 3 references

[3] doi:10.3390/ijms27146196

Investigation of the Potential Neuroprotective Mechanisms of <i>Acalypha indica</i> Against Alzheimer's Disease by Integrated Bioinformatics Analysis.

Journal: International journal of molecular sciences

In common: NCBI GEO GSE33000, Alzheimer's / dementia, genetics / omics, cellular / molecular

[4] doi:10.3390/biomedicines14050998 [code]

Integrative Multi-Omics and Machine Learning Analysis Identifies Therapeutic Targets and Drug Repurposing Candidates for Alzheimer's Disease.

Journal: Biomedicines

In common: NCBI GEO GSE33000, Alzheimer's / dementia, genetics / omics, cellular / molecular

[5] doi:10.1016/j.apsb.2026.04.017

PYGL-driven glycogenolysis impairs microglial autophagic flux <i>via</i> SNAP29 <i>O</i>-GlcNAcylation in Alzheimer's disease.

Journal: Acta pharmaceutica Sinica. B

In common: NCBI GEO GSE33000, Alzheimer's / dementia, cellular / molecular

[6] doi:10.1016/j.ynirp.2026.100366 [code]

Lower resting-state functional connectivity between frontoparietal and sensory networks is associated with recent pain intensity in a community sample of youth.

Journal: Neuroimage. Reports

In common: pain, 2 references

[7] doi:10.1038/s41467-026-71963-2 [code]

Spinal cord structural and functional architecture and its shared organization with the brain across the adult lifespan.

Journal: Nature communications

In common: 2 references

[8] doi:10.1186/s13024-026-00946-0

Insulin resistance alters cortical inhibitory neurons and microglia to exacerbate Alzheimer's knock-in mouse phenotypes.

Journal: Molecular neurodegeneration

In common: Alzheimer's / dementia, genetics / omics, mouse, 1 other category, 1 reference

[9] doi:10.1172/jci.insight.191905

The contribution of stem cell factor and its receptor c-Kit to cancer-induced bone pain.

Journal: JCI insight

In common: pain, mouse, cellular / molecular, 1 reference

[10] doi:10.3390/antiox15070807

Betaine Attenuates Hyperhomocysteinemia-Induced Cognitive Impairment by Suppressing Oxidative Stress and Activating the PI3K/AKT/GSK-3β Pathway.

Journal: Antioxidants (Basel, Switzerland)

In common: Alzheimer's / dementia, mouse, cellular / molecular, 1 reference

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.