Identification of early Alzheimer's disease subclass and signature genes based on PANoptosis genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39650656", "kind": "science-record", "revision": 4, "content_hash": "sha256:d52574349b4b6921068752b83cc715fc20fbe588c8806a3d9b13c8ec8fb5efcb", "created_at": "2026-11-01T20:29:56Z", "updated_at": "2026-11-01T22:55:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of early Alzheimer's disease subclass and signature genes based on PANoptosis genes.", "doi": "10.3389/fimmu.2024.1462003", "pmid": "39650656", "authors": ["Wenxu Wang", "Jincheng Lu", "Ningyun Pan", "Huiying Zhang", "Jingcen Dai", "Jie Li", "Cheng Chi", "Liumei Zhang", "Liang Wang", "Mengying Zhang"], "journal": "Frontiers in immunology", "year": 2024, "abstract": "Introduction: Alzheimer's disease (AD) is one of the most prevalent forms of dementia globally and remains an incurable condition that often leads to death. PANoptosis represents an emerging paradigm in programmed cell death, integrating three critical processes: pyroptosis, apoptosis, and necroptosis. Studies have shown that apoptosis, necroptosis, and pyroptosis play important roles in AD development. Therefore, targeting PANoptosis genes might lead to novel therapeutic targets and clinically relevant therapeutic approaches. This study aims to identify different molecular subtypes of AD and potential drugs for treating AD based on PANoptosis.\nMethods: Differentially expressed PANoptosis genes associated with AD were identified via Gene Expression Omnibus (GEO) dataset GSE48350, GSE5281, and GSE122063. Least Absolute Shrinkage and Selection Operator (LASSO) regression was employed to construct a risk model linked to these PANoptosis genes. Consensus clustering analysis was conducted to define AD subtypes based on these genes. We further performed gene set variation analysis (GSVA), functional enrichment analysis, and immune cell infiltration analysis to investigate differences between the identified AD subtypes. Additionally, a protein-protein interaction (PPI) network was established to identify hub genes, and the DGIdb database was consulted to identify potential therapeutic compounds targeting these hub genes. Single-cell RNA sequencing analysis was utilized to assess differences in gene expression at the cellular level across subtypes.\nResults: A total of 24 differentially expressed PANoptosis genes (APANRGs) were identified in AD, leading to the classification of two distinct AD subgroups. The results indicate that these subgroups exhibit varying disease progression states, with the early subtype primarily linked to dysfunctional synaptic signaling. Furthermore, we identified hub genes from the differentially expressed genes (DEGs) between the two clusters and predicted 38 candidate drugs and compounds for early AD treatment based on these hub genes. Single-cell RNA sequencing analysis revealed that key genes associated with the early subtype are predominantly expressed in neuronal cells, while the differential genes for the metabolic subtype are primarily found in endothelial cells and astrocytes.\nConclusion: In summary, we identified two subtypes, including the AD early synaptic abnormality subtype as well as the immune-metabolic subtype. Additionally, ten hub genes, SLC17A7, SNAP25, GAD1, SLC17A6, SLC32A1, PVALB, SYP, GRIN2A, SLC12A5, and SYN2, were identified as marker genes for the early subtype. These findings may provide valuable insights for the early diagnosis of AD and contribute to the development of innovative therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes in the GSE48350, GSE122063, and GSE5281 datasets were identified using the “limma” (20) R package with |Log2FC| > 0.1375, |Log2FC| > 0.5, and |Log2FC| > 0.5, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39650656", "locator": "sections[4] \"Identification of differentially expressed PANoptosis−related genes\" paragraph 2", "quote": "Differentially expressed genes in the GSE48350, GSE122063, and GSE5281 datasets were identified using the “limma” (20) R package with |Log2FC| > 0.1375, |Log2FC| > 0.5, and |Log2FC| > 0.5, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39650656", "locator": "sections[30] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 24 differentially expressed PANoptosis genes were identified in AD, leading to the classification of two distinct AD subgroups.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39650656", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 24 differentially expressed PANoptosis genes (APANRGs) were identified in AD, leading to the classification of two distinct AD subgroups."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 24 differentially expressed PANoptosis genes were identified in AD, leading to the classification of two distinct AD subgroups.", "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:39650656"], "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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