Identification of Plasma Cell Subsets and Molecular Markers of Alzheimer's Disease Based on Single-Cell Weighted Gene Co-Expression Network Analysis, Mendelian Randomization Analysis and Clinical Validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40994885", "kind": "science-record", "revision": 2, "content_hash": "sha256:4a8b1e0d78b5c12a4c9eac2e65e4c9ca9172f6f0ef63e0a228b8219d366cd57b", "created_at": "2026-11-01T20:31:04Z", "updated_at": "2026-11-01T21:35:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Plasma Cell Subsets and Molecular Markers of Alzheimer's Disease Based on Single-Cell Weighted Gene Co-Expression Network Analysis, Mendelian Randomization Analysis and Clinical Validation.", "doi": "10.2147/IJGM.S539547", "pmid": "40994885", "authors": ["Chao Xin", "Hong-Wei Zhi", "Da-Hua Wu", "Peng-Li Ding", "Zhong-Lin Wang", "Ya-Han Wang"], "journal": "International journal of general medicine", "year": 2025, "abstract": "Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gene expression alterations and immune dysregulation.\nMethods: In this study, we downloaded the GSE181279 single-cell dataset from the Gene Expression Omnibus (GEO) and applied bioinformatic analysis and clinical subject validation.\nResults: After quality control and harmony integration, we identified 21 cell subsets, including T cells, B cells, plasma cells, and macrophages. Plasma cells were significantly elevated in AD patients, and six plasma cell subtypes were associated with AD. High-dimensional weighted gene co-expression network analysis (hdWGCNA) revealed two AD-related modules. Mendelian randomization identified RGS1 as a key risk gene (p = 0.0123). Immune infiltration analysis showed RGS1 negatively correlated with macrophages and positively with tumor-infiltrating lymphocytes. Functional enrichment indicated that RGS1 is involved in JAK-STAT, NF-κB, and Wnt-β-catenin signaling pathways, suggesting a role in immune regulation and neuroinflammation. Furthermore, validation in AD patients confirmed that RGS1 expression levels were higher than in controls (p < 0.01).\nDiscussion: This study identified the key gene RGS1 related to AD and explored multiple signaling pathways associated with it, which provided important clues for the research on AD-related inflammation, gut microbiota, stretch-gated ion channel, and the evaluation of AD therapeutic targets.\nClinical Trial Registration Number: CTR20210477.", "claims": [{"id": "claim-method", "statement": "Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode (or Wald ratio if there was only one SNP in the causal relationship) were used to evaluate the reliability of the causal relationship and obtain an overall estimate of the effect of all cis isomers and cross-regional gene expression on AD using whole blood samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40994885", "locator": "sections[8] \"Mendelian Randomization (MR) Analysis\" paragraph 2", "quote": "Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode (or Wald ratio if there was only one SNP in the causal relationship) were used to evaluate the reliability of the causal relationship and obtain an overall estimate of the effect of all cis isomers and cross-regional gene expression on AD using whole blood samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are not publicly available because they protect patient privacy but are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40994885", "locator": "sections[32] \"Data Sharing Statement\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are not publicly available because they protect patient privacy but are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "RGS1 was identified as a key AD-related gene, and its expression was significantly higher in AD patients than in controls.", "kind": "quantitative", "target": {"value": 0.01, "unit": "p-value", "tolerance": null, "source": "Furthermore, validation in AD patients confirmed that RGS1 expression levels were higher than in controls (p < 0.01)."}, "evidence": [{"asset": "source:pmid:40994885", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study identified the key gene RGS1 related to AD and explored multiple signaling pathways associated with it, which provided important clues for the research on AD-related inflammation, gut microbiota, stretch-gated ion channel, and the evaluation of AD therapeutic targets."}, {"asset": "source:pmid:40994885", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Furthermore, validation in AD patients confirmed that RGS1 expression levels were higher than in controls (p < 0.01)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "RGS1 was identified as a key AD-related gene, and its expression was significantly higher in AD patients than in controls.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40994885"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The RT-qPCR results (Figure 15) showed that the relative", "hose of the control group (p < 0.01). The RT-qPCR results (Figure 15) showed that the relative"], "order_basis": "paper_text_order:4231", "id": "assay:1"}, {"role": "analysis", "definition_id": "genetic_association", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["mr_estimate"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode (or Wald ratio if there was only one SNP in the causal relationship) were used to evaluate the reliability of the causal relationship and obtain an overall estimate of the effect of all cis isomers and cross-regional gene expression on AD using whole blood samples."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}