5ededc25b844a622202fd2ea9960b71f pmc_33450872.pdf 2daa3f903893d04406ac50ade3722597ae17363a pmc_33450872.pdf 9fb6d4c55bfc2df64cfc139c9033f7c56220e0fcff74f1c7996a3ebaaa6ce87d pmc_33450872.pdf Title: Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease Subject: Lewy body diseases (LBD) including dementia with Lewy bodies (DLB) and Parkinson disease (PD) are characterized by alpha-synuclein pathology. DLB is difficult to diagnose and peripheral biomarkers are urgently needed. Therefore, we analyzed the expression of five alpha-synuclein gene (SNCA) transcripts, SNCAtv1, SNCAtv2, SNCAtv3, SNCA126, and SNCA112, in 45 LBD and control temporal cortex samples and in the blood of 72 DLB, 59 PD, and 54 control subjects. The results revealed overexpression of SNCAtv1 and SNCA112 in DLB, and SNCAtv2 in PD temporal cortices. In DLB blood, diminution of all SNCA transcripts was observed. SNCAtv1 and SNCAtv2 were diminished in PD with disease onset before 70 years. SNCAtv3, driven by its own promoter, showed opposite expression in early DLB and PD, suggesting that its amount may be an early, DLB specific biomarker. Correlation between blood transcript levels and disease duration was positive in DLB and negative in PD, possibly reflecting differences in brain alpha-synuclein aggregation rates associated with differences in disease courses. In conclusion, SNCA transcripts showed a disease-specific increase in the brain and were diminished in blood of LBD patients. SNCAtv3 expression was decreased in early DLB and increased in early PD and could be a biomarker for early DLB diagnosis. Keywords: alpha-synuclein; SNCA transcript variants; dementia with Lewy bodies; Parkinson’s disease; differential mRNA transcript expression; peripheral biomarker; disease progression Author: Laura Marsal-García, Aintzane Urbizu, Laura Arnaldo, Jaume Campdelacreu, Dolores Vilas, Lourdes Ispierto, Jordi Gascón-Bayarri, Ramón Reñé, Ramiro Álvarez and Katrin Beyer Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Mon Jan 18 07:26:23 2021 CET ModDate: Mon Jan 18 08:12:45 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2865871 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OHKNFJ+VnURWPalladioL Type 1 Custom yes yes no 10 0 UBYJNH+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 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WinAnsi yes yes no 253 0 ABCDEE+Palatino Linotype,Bold CID TrueType Identity-H yes yes yes 257 0 ABCDEE+Palatino Linotype CID TrueType Identity-H yes yes yes 264 0 MPUDFL+PazoMath Type 1 Builtin yes yes no 276 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:35:06 CEST RepresentationInformation: pmc_33450872.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:08:34 CEST Size: 2865871 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 496 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: Characteristics of Post-Mortem Cases Destination: subsection.2.1 Item: Title: Demographic and Clinical Data of Participants Destination: subsection.2.2 Item: Title: Relative SNCA Isoform Expression Levels in Different Brain Regions and Blood Destination: subsection.2.3 Item: Title: SNCA Transcript Expression in the Temporal Cortex Destination: subsection.2.4 Item: Title: Correlation between the Expression of SNCA Transcript Variants in Brain Destination: subsection.2.5 Item: Title: SNCA Transcript Expression in Blood Destination: subsection.2.6 Item: Title: Correlation between SNCA Transcript Expression, Disease Duration and Age-at-Onset in Blood Destination: subsection.2.7 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Source of Tissues Destination: subsection.4.1 Item: Title: Participants Destination: subsection.4.2 Item: Title: RNA Purification, Reverse Transcription, and Assessment of mRNA Stability Destination: subsection.4.3 Item: Title: Primer Design Destination: subsection.4.4 Item: Title: Real Time PCR Destination: subsection.4.5 Item: Title: Statistical Analysis Destination: subsection.4.6 Item: Title: References Destination: subsection.4.6 Info: Title: Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease Author: Laura Marsal-García, Aintzane Urbizu, Laura Arnaldo, Jaume Campdelacreu, Dolores Vilas, Lourdes Ispierto, Jordi Gascón-Bayarri, Ramón Reñé, Ramiro Álvarez and Katrin Beyer Subject: Lewy body diseases (LBD) including dementia with Lewy bodies (DLB) and Parkinson disease (PD) are characterized by alpha-synuclein pathology. DLB is difficult to diagnose and peripheral biomarkers are urgently needed. Therefore, we analyzed the expression of five alpha-synuclein gene (SNCA) transcripts, SNCAtv1, SNCAtv2, SNCAtv3, SNCA126, and SNCA112, in 45 LBD and control temporal cortex samples and in the blood of 72 DLB, 59 PD, and 54 control subjects. The results revealed overexpression of SNCAtv1 and SNCA112 in DLB, and SNCAtv2 in PD temporal cortices. In DLB blood, diminution of all SNCA transcripts was observed. SNCAtv1 and SNCAtv2 were diminished in PD with disease onset before 70 years. SNCAtv3, driven by its own promoter, showed opposite expression in early DLB and PD, suggesting that its amount may be an early, DLB specific biomarker. Correlation between blood transcript levels and disease duration was positive in DLB and negative in PD, possibly reflecting differences in brain alpha-synuclein aggregation rates associated with differences in disease courses. In conclusion, SNCA transcripts showed a disease-specific increase in the brain and were diminished in blood of LBD patients. SNCAtv3 expression was decreased in early DLB and increased in early PD and could be a biomarker for early DLB diagnosis. 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