{"doi":"10.1101/2021.12.22.21267952","title":"Transcriptome deregulation of peripheral monocytes in <i>GBA</i> -related Parkinson’s disease","abstract":"Abstract Background Genetic mutations in the beta-glucocerebrosidase (GCase), GBA gene, represent the major genetic risk factor for Parkinson’s disease (PD). The function of the GBA gene is at the crossroads between the endo-lysosomal pathway and the immune response, two important mechanisms involved in the pathogenesis of PD. However, modifiers of GBA penetrance have not yet been fully elucidated. Methods we characterized the transcriptomic profiles of circulating monocytes and whole blood in a population of patients with PD and healthy controls (CTRL) with (PD/GBA and CTRL/GBA) and without GBA variants (iPD and CTRL) (monocytes: n = 56 iPD, 66 CTRL, 23 PD/GBA, 13 CTRL/GBA; whole blood: n = 616 iPD, 362 CTRLs, 127 PD/GBA, 165 CTRL/GBA). Differential expression analysis, pathways enrichment analysis, and outliers detections were performed. Ultrastructural characterization of isolated CD14+ monocytes in the four groups was also performed through electron microscopy. Results We observed hundreds of differentially expressed genes and dysregulated pathways when comparing manifesting and non-manifesting GBA mutation carriers. Specifically, when compared to idiopathic PD, GBA-PD showed dysregulation in genes involved in alpha-synuclein degradation, aging and amyloid processing (i.e. SNCA, LMNA). Gene-based outlier analysis confirmed the involvement of lysosomal, membrane trafficking, and mitochondrial processing in manifesting compared to non-manifesting GBA -carriers, as also observed at the ultrastructural levels. Conclusions Overall, our transcriptomic analysis of primary monocytes identified gene targets and biological processes that can help in understanding the pathogenic mechanisms associated with GBA mutations in the context of PD.","journal":"medRxiv","year":2021,"id":219680,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":554051,"name":"Ricardo A. Vialle","orcid":"0000-0003-3311-4197","position":1,"is_corresponding":false},{"id":487898,"name":"Elisa Navarro","orcid":"0000-0002-4056-7146","position":2,"is_corresponding":false},{"id":487899,"name":"Evan Udine","orcid":"0000-0003-2509-0420","position":3,"is_corresponding":false},{"id":550555,"name":"Kátia de Paiva Lopes","orcid":"0000-0002-0240-0126","position":4,"is_corresponding":false},{"id":554050,"name":"Amanda Allan","orcid":"0000-0002-7627-4126","position":5,"is_corresponding":false},{"id":487901,"name":"Madison Parks","orcid":"0000-0002-7645-6130","position":6,"is_corresponding":false},{"id":312852,"name":"Brooklyn Henderson","orcid":null,"position":7,"is_corresponding":false},{"id":818399,"name":"Kelly Astudillo","orcid":"0000-0002-5697-0968","position":8,"is_corresponding":false},{"id":662545,"name":"Charalambos Argyrou","orcid":null,"position":9,"is_corresponding":false},{"id":662544,"name":"Maojuan Zhuang","orcid":null,"position":10,"is_corresponding":false},{"id":661646,"name":"Tamjeed Sikder","orcid":"0000-0001-5353-9884","position":11,"is_corresponding":false},{"id":818863,"name":"Oriol J. Narcis","orcid":null,"position":12,"is_corresponding":false},{"id":818864,"name":"Shilpa Dilip Kumar","orcid":null,"position":13,"is_corresponding":false},{"id":284300,"name":"William G.M. Janssen","orcid":"0000-0003-3954-7866","position":14,"is_corresponding":false},{"id":659533,"name":"Allison Sowa","orcid":null,"position":15,"is_corresponding":false},{"id":230738,"name":"Giacomo P. Comi","orcid":"0000-0002-1383-5248","position":16,"is_corresponding":false},{"id":112967,"name":"Alessio Di Fonzo","orcid":"0000-0001-6478-026X","position":17,"is_corresponding":false},{"id":308308,"name":"John F. Crary","orcid":"0000-0002-0556-293X","position":18,"is_corresponding":false},{"id":661649,"name":"Steven J. Frucht","orcid":"0000-0002-4653-0491","position":19,"is_corresponding":false},{"id":15885,"name":"Towfique Raj","orcid":"0000-0002-9355-5704","position":20,"is_corresponding":false},{"id":661645,"name":"Giulietta Riboldi","orcid":"0000-0003-0322-5718","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-18T23:53:38.409982Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}