{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T05:26:44Z","timestamp":1763702804704,"version":"3.45.0"},"reference-count":57,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spain\u2019s Ministry of Science and Innovation","award":["PI21\/00833","PI21\/00886","PMP22\/00100","PI24\/00214"],"award-info":[{"award-number":["PI21\/00833","PI21\/00886","PMP22\/00100","PI24\/00214"]}]},{"DOI":"10.13039\/501100004587","name":"ISCIII","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Platelets are increasingly recognized as multifunctional cells with roles extending beyond hemostasis to immune regulation, inflammation, and neurodegeneration. Here, we performed RNA-Seq profiling of platelets from patients with idiopathic REM sleep behavior disorder (IRBD), dementia with Lewy bodies (DLB), Parkinson disease (PD), Alzheimer disease (AD), and healthy controls (CTRLs) to explore disease-specific transcriptomic signatures. Across all groups, the RNA class distribution was similar, dominated by mRNAs (78\u201380%) and long non-coding RNAs (lncRNAs; 15\u201316%). DLB platelets displayed a reduced proportion of lncRNAs, suggesting an impaired RNA regulation, whereas IRBD concentrated the highest number of disease-specific lncRNAs, half of which were Y-linked, consistent with the male predominance observed in alpha-synucleinopathies. Differential expression analysis (DEA) revealed extensive transcriptomic remodeling in IRBD and DLB, particularly affecting RNA processing, cytoskeletal organization, and platelet activation pathways, while PD and AD showed minimal changes. These findings suggest a progressive impairment of platelet activation and signaling across the DLB continuum, potentially mirroring neuronal dysfunction. The limited transcriptional deregulation in PD may reflect its pronounced biological heterogeneity, consistent with recent multidimensional disease models. Overall, our study highlights platelets as accessible indicators of early and disease-stage-specific molecular alterations in \u03b1-synucleinopathies.<\/jats:p>","DOI":"10.3390\/ijms262211169","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T11:17:27Z","timestamp":1763551047000},"page":"11169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Does Platelet Transcriptome Dysregulation Across the Lewy Body Continuum Mirror Neuronal Dysfunction?"],"prefix":"10.3390","volume":"26","author":[{"given":"Laura","family":"Arnaldo","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Research Institute Germans Trias i Pujol, 08916 Badalona, Spain"},{"name":"Departament de Bioqu\u00edmica i de Biologia Molecular, Facultat de Bioci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4524-205X","authenticated-orcid":false,"given":"Jorge","family":"Mena","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Research Institute Germans Trias i Pujol, 08916 Badalona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0326-5991","authenticated-orcid":false,"given":"David","family":"Adamuz","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Research Institute Germans Trias i Pujol, 08916 Badalona, Spain"},{"name":"Facultat de Medicina, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol Badalona, 08916 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1532-1278","authenticated-orcid":false,"given":"M\u00f2nica","family":"Serradell","sequence":"additional","affiliation":[{"name":"Sleep Unit, Department of Neurology, Hospital Cl\u00ednic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Samaniego","sequence":"additional","affiliation":[{"name":"Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol Badalona, 08916 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carles","family":"Gaig","sequence":"additional","affiliation":[{"name":"Sleep Unit, Department of Neurology, Hospital Cl\u00ednic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Ispierto","sequence":"additional","affiliation":[{"name":"Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol Badalona, 08916 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Vilas","sequence":"additional","affiliation":[{"name":"Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol Badalona, 08916 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Iranzo","sequence":"additional","affiliation":[{"name":"Sleep Unit, Department of Neurology, Hospital Cl\u00ednic de Barcelona, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED), 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Centre for Age-Related Medicine (SESAM), Stavanger University Hospital, 4068 Stavanger, Norway"},{"name":"Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 8AB, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pau","family":"Pastor","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Research Institute Germans Trias i Pujol, 08916 Badalona, Spain"},{"name":"Unit of Neurodegenerative Diseases, Department of Neurology, University Hospital Germans Trias i Pujol Badalona, 08916 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-1514","authenticated-orcid":false,"given":"Katrin","family":"Beyer","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Research Institute Germans Trias i Pujol, 08916 Badalona, Spain"},{"name":"Facultat de Medicina, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"GBD 2019 Dementia Forecasting Collaborators. 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