Does Platelet Transcriptome Dysregulation Across the Lewy Body Continuum Mirror Neuronal Dysfunction?
Arnaldo, Laura (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Mena, Jorge (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Adamuz , David (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Menéndez Albarracín, Alex (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Serradell, Mònica (Hospital Clínic i Provincial de Barcelona)
Samaniego-Toro, Daniela (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Gaig, Carles (Hospital Clínic i Provincial de Barcelona)
Ispierto, Lourdes (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vilas Rolán, Dolores (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Iranzo, Alex (Hospital Clínic i Provincial de Barcelona)
Aarsland, Dag (King's College London)
Pastor, Pau (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Beyer, Katrin (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2025
Resum:	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 (78-80%) and long non-coding RNAs (lncRNAs; 15-16%). 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 α-synucleinopathies.
Ajuts:	Instituto de Salud Carlos III PI21/00833 Instituto de Salud Carlos III PI21/00886 Instituto de Salud Carlos III PMP22/00100
Nota:	This research was funded by Spain\u2019s Ministry of Science and Innovation, grant number PI21/00833, PI21/00886, PMP22/00100 and PI24/00214, integrated in the National R + D + I and funded by the ISCIII and the European Regional Development Fund.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Platelet transcriptome ; Dementia with Lewy bodies ; Parkinson's disease ; Alzheimer's disease ; Idiopathic REM sleep behavior disorder ; RNA sequencing ; Differential gene expression
Publicat a:	International journal of molecular sciences, Vol. 26, Num. 22 (November 2025) , art. 11169, ISSN 1422-0067

DOI: 10.3390/ijms262211169
PMID: 41303651

26 p, 3.0 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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