Skip to content
DraconiticResearch
Search Sources API
186,125 studies31 sourcesUpdated 34 min ago
Peer-reviewedCC BY 4.0Advanced Science

Systematic Multi‐Level Analyses Decode the Arthritis‐Neurodegeneration Axis With In Vivo Validation

  • Jinwen Wang1
  • Wenhui Xie2
  • Lei Yang3
  • Zhengrong Wang1
  • Yi Huang1
  • Peng Huang4
  • Yuan Liu3
  • Jun Hu1
4 affiliations
  1. 1Department of Orthopedics The First Affiliated Hospital with Nanjing Medical University Nanjing China
  2. 2Department of Biostatistics School of Public Health Nanjing Medical University Nanjing China
  3. 3Department of Infectious Diseases The First Affiliated Hospital with Nanjing Medical University Nanjing China
  4. 4Department of Epidemiology Center For Global Health School of Public Health Nanjing Medical University Nanjing China
Read full textDOICite

Abstract

Arthritis may influence neurodegenerative risk, but directionality and mediators remain unclear. This study integrates population survival analysis, Mendelian randomization, transcriptomic mapping, and mouse perturbation to map osteoarthritis (OA)/rheumatoid arthritis (RA) links with five neurodegenerative outcomes and prioritize mediators. In 310 162 European‐ancestry UK Biobank participants, Cox models associate OA with higher risks of Alzheimer's disease (AD; hazard ratio: 1.13, 95% confidence interval: 1.04–1.22), Parkinson's disease (PD; 1.10, 1.00–1.21), and disorders of autonomic nervous system (DANS; 1.36, 1.06–1.74), and RA with higher AD risk (1.37, 1.13–1.67) (all p < 0.05), but not incident PD. Mendelian randomization prioritizes a modest protective genetic effect of RA on PD (odds ratio: 0.93, 0.88–0.99; p = 0.015), without reverse causation. Transcriptome‐wide association and colocalization analyses identify shared RA–PD genes and prioritize Ring Finger Protein 40 (RNF40). In a collagen‐induced arthritis (CIA) and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model, CIA attenuates dopaminergic injury, whereas systemic Rnf40 knockdown alleviates arthritis but exacerbates Parkinsonian pathology. Endogenous RNF40 is induced in arthritic joints but remains stable in midbrain. These cross‐layer data define arthritis–neurodegeneration connections and nominate RNF40 as a context‐dependent joint–brain candidate linking inflammatory arthritis with dopaminergic vulnerability.

Related

  1. Validation of the Brief-Cope Questionnaire in a Seropositive Rheumatoid Arthritis Population
    I. Iliadis, I. Heitland, K. Hoeper +4
    medRxivPreprintAll rights reservedFull textGeneral medicinemedRxiv
  2. XuanBi Mitigates Rheumatoid Arthritis via Regulation of ECM‐Receptor Interactions and IL‐17 Signaling: Insights From Integrated Proteomic and Pharmacological Analyses
    Hao Zhu, Zhenfeng Pan, Ying Lu +6
    Food Science & NutritionPeer-reviewedCC BY 4.0Full textGeneral medicinePMCEurope PMC
  3. Performance of the Expanded Cardiovascular Risk Prediction Score for Rheumatoid Arthritis: An External Validation of the BRASS Registry
    Misti L. Paudel, Katherine Liao, Jon T. Giles +8
    Arthritis care & researchPeer-reviewedLicence not statedFull textGeneral medicinePMC
  4. Multifactorial lifestyle interventions in rheumatoid arthritis: a systematic literature review
    Megan Curran, Kevin Durkan, Afroja Ahmed +3
    EULAR rheumatology openPeer-reviewedCC BYFull textGeneral medicineEurope PMC
  5. Screening for rheumatoid arthritis-associated interstitial lung disease using lung ultrasound: a systematic review and quality appraisal of recent studies
    A. D. Copoeru, M. Mocan, A. Farcas +2
    medRxivPreprintAll rights reservedFull textGeneral medicinemedRxiv

Cite

BibTeXRIS
BibTeX
@article{wang2026systematic,
  title = {{Systematic Multi‐Level Analyses Decode the Arthritis‐Neurodegeneration Axis With In Vivo Validation}},
  author = {Jinwen Wang and Wenhui Xie and Lei Yang and Zhengrong Wang and Yi Huang and Peng Huang and Yuan Liu and Jun Hu},
  journal = {Advanced Science},
  year = {2026},
  month = aug,
  doi = {10.1002/advs.76930},
  url = {https://doi.org/10.1002/advs.76930},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Systematic Multi‐Level Analyses Decode the Arthritis‐Neurodegeneration Axis With In Vivo Validation
AU  - Jinwen Wang
AU  - Wenhui Xie
AU  - Lei Yang
AU  - Zhengrong Wang
AU  - Yi Huang
AU  - Peng Huang
AU  - Yuan Liu
AU  - Jun Hu
PY  - 2026
DA  - 2026/08/05
JO  - Advanced Science
DO  - 10.1002/advs.76930
UR  - https://doi.org/10.1002/advs.76930
AB  - Arthritis may influence neurodegenerative risk, but directionality and mediators remain unclear. This study integrates population survival analysis, Mendelian randomization, transcriptomic mapping, and mouse perturbation to map osteoarthritis (OA)/rheumatoid arthritis (RA) links with five neurodegenerative outcomes and prioritize mediators. In 310 162 European‐ancestry UK Biobank participants, Cox models associate OA with higher risks of Alzheimer's disease (AD; hazard ratio: 1.13, 95% confidence interval: 1.04–1.22), Parkinson's disease (PD; 1.10, 1.00–1.21), and disorders of autonomic nervous system (DANS; 1.36, 1.06–1.74), and RA with higher AD risk (1.37, 1.13–1.67) (all p < 0.05), but not incident PD. Mendelian randomization prioritizes a modest protective genetic effect of RA on PD (odds ratio: 0.93, 0.88–0.99; p = 0.015), without reverse causation. Transcriptome‐wide association and colocalization analyses identify shared RA–PD genes and prioritize Ring Finger Protein 40 (RNF40). In a collagen‐induced arthritis (CIA) and 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model, CIA attenuates dopaminergic injury, whereas systemic Rnf40 knockdown alleviates arthritis but exacerbates Parkinsonian pathology. Endogenous RNF40 is induced in arthritic joints but remains stable in midbrain. These cross‐layer data define arthritis–neurodegeneration connections and nominate RNF40 as a context‐dependent joint–brain candidate linking inflammatory arthritis with dopaminergic vulnerability.
SN  - 2198-3844
ER  -