Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer's disease through a systems biology approach and drug repurposing.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38809924", "kind": "science-record", "revision": 3, "content_hash": "sha256:1b1dcec94ae71edf7e995c0e0e277d400b6c46c0070b6e4b062e4e695c7e2cce", "created_at": "2026-11-01T19:20:46Z", "updated_at": "2026-11-01T22:11:57Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Deciphering molecular bridges: Unveiling the interplay between metabolic syndrome and Alzheimer's disease through a systems biology approach and drug repurposing.", "doi": "10.1371/journal.pone.0304410", "pmid": "38809924", "authors": ["Zahra Azizan", "Hakimeh Zali", "Seyed Amir Mirmotalebisohi", "Maryam Bazrgar", "Abolhassan Ahmadiani"], "journal": "PloS one", "year": 2024, "abstract": "The association between Alzheimer's disease and metabolic disorders as significant risk factors is widely acknowledged. However, the intricate molecular mechanism intertwining these conditions remains elusive. To address this knowledge gap, we conducted a thorough investigation using a bioinformatics method to illuminate the molecular connections and pathways that provide novel perspectives on these disorders' pathological and clinical features. Microarray datasets (GSE5281, GSE122063) from the Gene Expression Omnibus (GEO) database facilitated the way to identify genes with differential expression in Alzheimer's disease (141 genes). Leveraging CoreMine, CTD, and Gene Card databases, we extracted genes associated with metabolic conditions, including hypertension, non-alcoholic fatty liver disease, and diabetes. Subsequent analysis uncovered overlapping genes implicated in metabolic conditions and Alzheimer's disease, revealing shared molecular links. We utilized String and HIPPIE databases to visualize these shared genes' protein-protein interactions (PPI) and constructed a PPI network using Cytoscape and MCODE plugin. SPP1, CD44, IGF1, and FLT1 were identified as crucial molecules in the main cluster of Alzheimer's disease and metabolic syndrome. Enrichment analysis by the DAVID dataset was employed and highlighted the SPP1 as a novel target, with its receptor CD44 playing a significant role in the inflammatory cascade and disruption of insulin signaling, contributing to the neurodegenerative aspects of Alzheimer's disease. ECM-receptor interactions, focal adhesion, and the PI3K/Akt pathways may all mediate these effects. Additionally, we investigated potential medications by repurposing the molecular links using the DGIdb database, revealing Tacrolimus and Calcitonin as promising candidates, particularly since they possess binding sites on the SPP1 molecule. In conclusion, our study unveils crucial molecular bridges between metabolic syndrome and AD, providing insights into their pathophysiology for therapeutic interventions.", "claims": [{"id": "claim-method", "statement": "To validate the crucial genes that establish a connection between metabolic syndrome and AD, we performed the Fisher exact test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38809924", "locator": "sections[16] \"Identifying clusters in the AD PPI network and associating them with MetS conditions-related genes\" paragraph 2", "quote": "To validate the crucial genes that establish a connection between metabolic syndrome and AD, we performed the Fisher exact test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the manuscript and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38809924", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the manuscript and its Supporting Information files."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 141 common Alzheimer’s disease-associated differentially expressed genes from two GEO microarray datasets and identified SPP1, CD44, IGF1, and FLT1 as critical shared molecular links between Alzheimer’s disease and metabolic syndrome.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38809924", "locator": "sections[13] \"Data pre-processing and identification of AD-associated DEGs\" paragraph 2", "quote": "Using the Venn diagram tool, 141 common genes were identified as AD-associated DEGs, consisting of 43 upregulated and 98 downregulated genes (Fig 2G, S1 File)."}, {"asset": "source:pmid:38809924", "locator": "sections[15] \"PPI network of shared genes between AD and MetS conditions and identification of molecular links\" paragraph 4", "quote": "Consequently, we have identified FLT1, SPP1, CD44, and IGF1 as the critical genes shared among the clusters in the PPI network of AD and metabolic syndrome."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 141 common Alzheimer’s disease-associated differentially expressed genes from two GEO microarray datasets and identified SPP1, CD44, IGF1, and FLT1 as critical shared molecular links between Alzheimer’s disease and metabolic syndrome.", "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:38809924"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE122063"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE122063"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38809924", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0304410", "sha256": "sha256:c4dc1ed37fe5c6c82196cf1e06510c799970e7551504369e4aae65a19d9da4d2", "bytes": 46354, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0304410", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11135670", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE122063", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE122063", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE122063", "version": null, "note": "All relevant data are within the manuscript and its Supporting Information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All relevant data are within the manuscript and its Supporting Information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3454053", "GSM3454054", "GSM3454055", "GSM3454056", "GSM3454057", "GSM3454058", "GSM3454059", "GSM3454060", "GSM3454061", "GSM3454062", "GSM3454063", "GSM3454064", "GSM3454065", "GSM3454066", "GSM3454067", "GSM3454068", "GSM3454069", "GSM3454070", "GSM3454071", "GSM3454072", "GSM3454073", "GSM3454074", "GSM3454075", "GSM3454076", "GSM3454077", "GSM3454078", "GSM3454079", "GSM3454080", "GSM3454081", "GSM3454082", "GSM3454083", "GSM3454084", "GSM3454085", "GSM3454086", "GSM3454087", "GSM3454088", "GSM3454089", "GSM3454090", "GSM3454091", "GSM3454092", "GSM3454093", "GSM3454094", "GSM3454095", "GSM3454096", "GSM3454097", "GSM3454098", "GSM3454099", "GSM3454100", "GSM3454101", "GSM3454102", "GSM3454103", "GSM3454104", "GSM3454105", "GSM3454106", "GSM3454107", "GSM3454108", "GSM3454109", "GSM3454110", "GSM3454111", "GSM3454112", "GSM3454113", "GSM3454114", "GSM3454115", "GSM3454116", "GSM3454117", "GSM3454118", "GSM3454119", "GSM3454120", "GSM3454121", "GSM3454122", "GSM3454123", "GSM3454124", "GSM3454125", "GSM3454126", "GSM3454127", "GSM3454128", "GSM3454129", "GSM3454130", "GSM3454131", "GSM3454132", "GSM3454133", "GSM3454134", "GSM3454135", "GSM3454136", "GSM3454137", "GSM3454138", "GSM3454139", "GSM3454140", "GSM3454141", "GSM3454142", "GSM3454143", "GSM3454144", "GSM3454145", "GSM3454146", "GSM3454147", "GSM3454148", "GSM3454149", "GSM3454150", "GSM3454151", "GSM3454152", "GSM3454153", "GSM3454154", "GSM3454155", "GSM3454156", "GSM3454157", "GSM3454158", "GSM3454159", "GSM3454160", "GSM3454161", "GSM3454162", "GSM3454163", "GSM3454164", "GSM3454165", "GSM3454166", "GSM3454167", "GSM3454168", "GSM3454169", "GSM3454170", "GSM3454171", "GSM3454172", "GSM3454173", "GSM3454174", "GSM3454175", "GSM3454176", "GSM3454177", "GSM3454178", "GSM3454179", "GSM3454180", "GSM3454181", "GSM3454182", "GSM3454183", "GSM3454184", "GSM3454185", "GSM3454186", "GSM3454187", "GSM3454188"], "sample_count": 136, "group_sizes": null, "group_sizes_basis": null, "platform": "16699", "taxon": "Homo sapiens", "title": "Dementia Comparison: VaD vs. AD vs. Controls", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE5281", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5281", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE5281", "version": null, "note": "All relevant data are within the manuscript and its Supporting Information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All relevant data are within the manuscript and its Supporting Information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM119615", "GSM119616", "GSM119617", "GSM119618", "GSM119619", "GSM119620", "GSM119621", "GSM119622", "GSM119623", "GSM119624", "GSM119625", "GSM119626", "GSM119627", "GSM119628", "GSM119629", "GSM119630", "GSM119631", "GSM119632", "GSM119633", "GSM119634", "GSM119635", "GSM119636", "GSM119637", "GSM119638", "GSM119639", "GSM119640", "GSM119641", "GSM119642", "GSM119643", "GSM119644", "GSM119645", "GSM119646", "GSM119647", "GSM119648", "GSM119649", "GSM119650", "GSM119651", "GSM119652", "GSM119653", "GSM119654", "GSM119655", "GSM119656", "GSM119657", "GSM119658", "GSM119659", "GSM119660", "GSM119661", "GSM119662", "GSM119663", "GSM119664", "GSM119665", "GSM119666", "GSM119667", "GSM119668", "GSM119669", "GSM119670", "GSM119671", "GSM119672", "GSM119673", "GSM119674", "GSM119675", "GSM119676", "GSM119677", "GSM119678", "GSM119679", "GSM119680", "GSM119681", "GSM119682", "GSM119683", "GSM119684", "GSM119685", "GSM119686", "GSM119687", "GSM119688", "GSM238763", "GSM238790", "GSM238791", "GSM238792", "GSM238793", "GSM238794", "GSM238795", "GSM238796", "GSM238797", "GSM238798", "GSM238799", "GSM238800", "GSM238801", "GSM238802", "GSM238803", "GSM238804", "GSM238805", "GSM238806", "GSM238807", "GSM238808", "GSM238809", "GSM238810", "GSM238811", "GSM238812", "GSM238813", "GSM238815", "GSM238816", "GSM238817", "GSM238818", "GSM238819", "GSM238820", "GSM238821", "GSM238822", "GSM238823", "GSM238824", "GSM238825", "GSM238826", "GSM238827", "GSM238834", "GSM238835", "GSM238837", "GSM238838", "GSM238839", "GSM238840", "GSM238841", "GSM238842", "GSM238843", "GSM238844", "GSM238845", "GSM238846", "GSM238847", "GSM238848", "GSM238851", "GSM238854", "GSM238855", "GSM238856", "GSM238857", "GSM238858", "GSM238860", "GSM238861", "GSM238862", "GSM238863", "GSM238864", "GSM238865", "GSM238867", "GSM238868", "GSM238870", "GSM238871", "GSM238872", "GSM238873", "GSM238874", "GSM238875", "GSM238877", "GSM238941", "GSM238942", "GSM238943", "GSM238944", "GSM238945", "GSM238946", "GSM238947", "GSM238948", "GSM238949", "GSM238951", "GSM238952", "GSM238953", "GSM238955", "GSM238963"], "sample_count": 161, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Alzheimer's disease and the normal aged brain (steph-affy-human-433773)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE122063 not downloaded", "asset:data:geo:GSE122063 licence not read", "asset:data:geo:GSE5281 not downloaded", "asset:data:geo:GSE5281 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-2", "family": null, "specific": null, "label": "Fisher’s exact test", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To validate the crucial genes that establish a connection between metabolic syndrome and AD, we performed the Fisher exact test."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE5281", "GSE122063"], "resolved_accessions": ["GSE5281", "GSE122063"], "statements": ["All relevant data are within the manuscript and its Supporting Information files."], "basis": "The paper names GSE5281, GSE122063 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:38809924", "data:geo:GSE122063"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE122063"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:19:59Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13143, "completion_tokens": 1354, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:38809924", "type": "paper", "label": "pmid:38809924"}, {"id": "source:pmid:38809924", "type": "manuscript", "label": "PMID 38809924 full text"}, {"id": "data:geo:GSE122063", "type": "dataset", "label": "GEO GSE122063"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38809924", "type": "paper", "label": "pmid:38809924"}, {"id": "source:pmid:38809924", "type": "manuscript", "label": "PMID 38809924 full text"}, {"id": "data:geo:GSE122063", "type": "dataset", "label": "GEO GSE122063"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38809924", "type": "extraction", "used": ["source:pmid:38809924"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE122063", "type": "accession_resolution", "used": ["data:geo:GSE122063"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:38809924", "parent_hash": "sha256:4f0a40c39abdcd44002cb03a7f4689a2c7838fd45fc59b4d7aec4a4fab1b8a28", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE122063 licence not read", "asset:data:geo:GSE122063 not downloaded", "asset:data:geo:GSE5281 licence not read", "asset:data:geo:GSE5281 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["sorders' pathological and clinical features. Microarray datasets (GSE5281, GSE122063) from the Gene", "GEO (https://www.ncbi.nlm.nih.gov/geo/) for microarray datasets AD using the following search crite", "search criteria: \"Alzheimer’s disease\" and \"microarray\". We then applied inclusion criteria to sele", "tients and healthy controls≥60 yrs., and (4) microarray platform. GSE5281 contains 87 patients and 7"], "order_basis": "paper_text_order:568", "id": "assay:1"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["PPI"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}