Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease

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 (<i>SNCA&...

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Main Authors: Laura Marsal-García, Aintzane Urbizu, Laura Arnaldo, Jaume Campdelacreu, Dolores Vilas, Lourdes Ispierto, Jordi Gascón-Bayarri, Ramón Reñé, Ramiro Álvarez, Katrin Beyer
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/2/725
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author Laura Marsal-García
Aintzane Urbizu
Laura Arnaldo
Jaume Campdelacreu
Dolores Vilas
Lourdes Ispierto
Jordi Gascón-Bayarri
Ramón Reñé
Ramiro Álvarez
Katrin Beyer
author_facet Laura Marsal-García
Aintzane Urbizu
Laura Arnaldo
Jaume Campdelacreu
Dolores Vilas
Lourdes Ispierto
Jordi Gascón-Bayarri
Ramón Reñé
Ramiro Álvarez
Katrin Beyer
author_sort Laura Marsal-García
collection DOAJ
description 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 (<i>SNCA</i>) 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 <i>SNCA</i> 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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spelling doaj.art-a73f43b2b6834f16b92a420d1e9c02042023-12-03T13:01:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-0122272510.3390/ijms22020725Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s DiseaseLaura Marsal-García0Aintzane Urbizu1Laura Arnaldo2Jaume Campdelacreu3Dolores Vilas4Lourdes Ispierto5Jordi Gascón-Bayarri6Ramón Reñé7Ramiro Álvarez8Katrin Beyer9Department of Pathology, Germans Trias i Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, SpainDepartment of Pathology, Germans Trias i Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, SpainDepartment of Pathology, Germans Trias i Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, SpainServei de Neurologia, Hospital Universitari Bellvitge, 08907 L’Hospitalet de Llobregat, SpainServei de Neurologia, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, SpainServei de Neurologia, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, SpainServei de Neurologia, Hospital Universitari Bellvitge, 08907 L’Hospitalet de Llobregat, SpainServei de Neurologia, Hospital Universitari Bellvitge, 08907 L’Hospitalet de Llobregat, SpainServei de Neurologia, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, SpainDepartment of Pathology, Germans Trias i Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, SpainLewy 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 (<i>SNCA</i>) 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 <i>SNCA</i> 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.https://www.mdpi.com/1422-0067/22/2/725alpha-synucleinSNCA transcript variantsdementia with Lewy bodiesParkinson’s diseasedifferential mRNA transcript expressionperipheral biomarker
spellingShingle Laura Marsal-García
Aintzane Urbizu
Laura Arnaldo
Jaume Campdelacreu
Dolores Vilas
Lourdes Ispierto
Jordi Gascón-Bayarri
Ramón Reñé
Ramiro Álvarez
Katrin Beyer
Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease
International Journal of Molecular Sciences
alpha-synuclein
SNCA transcript variants
dementia with Lewy bodies
Parkinson’s disease
differential mRNA transcript expression
peripheral biomarker
title Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease
title_full Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease
title_fullStr Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease
title_full_unstemmed Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease
title_short Expression Levels of an Alpha-Synuclein Transcript in Blood May Distinguish between Early Dementia with Lewy Bodies and Parkinson’s Disease
title_sort expression levels of an alpha synuclein transcript in blood may distinguish between early dementia with lewy bodies and parkinson s disease
topic alpha-synuclein
SNCA transcript variants
dementia with Lewy bodies
Parkinson’s disease
differential mRNA transcript expression
peripheral biomarker
url https://www.mdpi.com/1422-0067/22/2/725
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