6a1cae3df407a7835a086d161f13cc2d 315609.pdf 808c47cf22b4a65b32d791d8ce63d63bb91c9ede 315609.pdf 6526d5d0c77cf0e7357d2c4b933d2bca3f96e10eb8eace750b7941227569f0f7 315609.pdf Title: Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease Subject: Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD. Keywords: Alzheimer disease; dementia with Lewy bodies; miRNA; peripheral biomarkers; platelets; synucleinopathies Author: Ana Gámez-Valero, Jaume Campdelacreu, Dolores Vilas, Lourdes Ispierto, Jordi Gascón-Bayarri, Ramón Reñé, Ramiro Álvarez, Maria P. Armengol, Francesc E. Borràs and Katrin Beyer Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Mon Sep 20 12:17:02 2021 CEST ModDate: Mon Sep 20 12:20:39 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2201355 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- MEXBTU+VnURWPalladioL Type 1 Custom yes yes no 10 0 BMUHVX+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 YWWZGH+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 YVDVEC+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 AAGRJJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 EBFBTV+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 58 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 62 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 66 0 VVSYYB+EURM10 Type 1 Builtin yes yes no 78 0 GJHLPN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 88 0 GJHLPP+PalatinoLinotype TrueType WinAnsi yes yes no 91 0 GJHMBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 94 0 UWJUYN+CMSY10 Type 1 Builtin yes yes no 101 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 108 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes no 115 0 GJHLPN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 127 0 GJHLPP+PalatinoLinotype TrueType WinAnsi yes yes no 130 0 GJHMBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 133 0 GJHLPN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 143 0 GJHLPP+PalatinoLinotype TrueType WinAnsi yes yes no 146 0 GJHMBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 149 0 GJHLPN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 173 0 GJHLPP+PalatinoLinotype TrueType WinAnsi yes yes no 176 0 GJHMBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 179 0 GJHLPN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 190 0 GJHLPP+PalatinoLinotype TrueType WinAnsi yes yes no 193 0 GJHMBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 196 0 GJHLPN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 211 0 GJHLPO+PalatinoLinotype CID TrueType Identity-H yes yes yes 214 0 GJHLPP+PalatinoLinotype TrueType WinAnsi yes yes no 220 0 GJHMBA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 223 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-07-25 02:54:27 CEST RepresentationInformation: 315609.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-07-24 14:31:42 CEST Size: 2201355 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 456 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Participants Destination: subsection.2.1 Item: Title: Blood Collection, Purification and Characterization of Platelets Destination: subsection.2.2 Item: Title: Purification of Platelet-Derived Small RNA Destination: subsection.2.3 Item: Title: MiRNA Isolation from Whole Blood Destination: subsection.2.4 Item: Title: Discovery Phase: miRNA Sequencing and Sequencing Data Analysis Destination: subsection.2.5 Item: Title: Validation Phase: Reverse Transcription and Quantitative Real-Time PCR Destination: subsection.2.6 Item: Title: Statistical Analysis Destination: subsection.2.7 Item: Title: miRNA Target Prediction and Analysis Destination: subsection.2.8 Item: Title: Results Destination: section.3 Children: Item: Title: Demographic and Clinical Data Destination: subsection.3.1 Item: Title: Platelet Characterization and miRNA Profile Discovery Destination: subsection.3.2 Item: Title: Validation of miRNA Expression Destination: subsection.3.3 Children: Item: Title: Study I (2017) Destination: subsubsection.3.3.1 Item: Title: Study II (2018) Destination: subsubsection.3.3.2 Item: Title: Study III (2019) Destination: subsubsection.3.3.3 Item: Title: ROC Curve Analysis Destination: subsection.3.4 Item: Title: miRNA Expression in Whole Blood Destination: subsection.3.5 Item: Title: miRNA Target Prediction Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: Patents Destination: section.6 Item: Title: References Destination: section.6 Info: Title: Platelet miRNA Biosignature Discriminates between Dementia with Lewy Bodies and Alzheimer’s Disease Author: Ana Gámez-Valero, Jaume Campdelacreu, Dolores Vilas, Lourdes Ispierto, Jordi Gascón-Bayarri, Ramón Reñé, Ramiro Álvarez, Maria P. Armengol, Francesc E. Borràs and Katrin Beyer Subject: Dementia with Lewy bodies (DLB) is one of the most common causes of degenerative dementia, after Alzheimer’s disease (AD), and presents pathological and clinical overlap with both AD and Parkinson’s disease (PD). Consequently, only one in three DLB cases is diagnosed correctly. Platelets, previously related to neurodegeneration, contain microRNAs (miRNAs) whose analysis may provide disease biomarkers. Here, we profiled the whole platelet miRNA transcriptome from DLB patients and healthy controls. Differentially expressed miRNAs were further validated in three consecutive studies from 2017 to 2019 enrolling 162 individuals, including DLB, AD, and PD patients, and healthy controls. Results comprised a seven-miRNA biosignature, showing the highest diagnostic potential for the differentiation between DLB and AD. Additionally, compared to controls, two miRNAs were down-regulated in DLB, four miRNAs were up-regulated in AD, and two miRNAs were down-regulated in PD. Predictive target analysis identified three disease-specific clusters of pathways as a result of platelet-miRNA deregulation. Our cross-sectional study assesses the identification of a novel, highly specific and sensitive platelet-associated miRNA-based biosignature, which distinguishes DLB from AD. 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