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 (SNCA) transcri...

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Authors: Marsal-García, Laura|||0000-0002-6337-1656, Campdelacreu, Jaume|||0000-0001-9196-7601, Vilas Rolán, Dolores|||0000-0003-3084-053X, Ispierto, Lourdes, Gascon Bayarri, Jordi|||0000-0002-9422-937X, Reñé, Ramón, Álvarez, Ramiro|||0000-0002-8053-7232, Beyer, Katrin|||0000-0001-8905-1514, Urbizu, Aintzane|||0000-0001-8458-1209, Arnaldo, Laura|||0000-0003-1654-0573
Format: article
Publication Date:2021
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:236291
Online Access:https://ddd.uab.cat/record/236291
https://dx.doi.org/urn:doi:10.3390/ijms22020725
Access Level:Open access
Keyword:Alpha-synuclein
SNCA transcript variants
Dementia with Lewy bodies
Parkinson's disease
Differential mRNA transcript expression
Peripheral biomarker
Disease progression
Description
Summary: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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