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New brain-specific beta-synuclein isoforms show expression ratio changes in Lewy body diseases

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Abstract

Lewy body diseases (LBDs) include dementia with Lewy bodies (DLB) and Parkinson disease (PD). Alpha-synuclein (AS) aggregation is a key event in the pathogenesis of LBDs and beta-synuclein (BS) inhibits AS aggregation in vitro and in vivo. Recently, BS has been shown to interact directly with AS regulating its functionality and preventing its oligomerization, and a molecular subgroup of pure DLB lacks BS in cortical regions. In this study, we characterized four new BS transcript variants and analyzed their expression in neuronal and non-neuronal tissue, and their differential expression in frozen samples of three areas from brains of patients with pure Lewy body pathology (LBP), common LBP, Alzheimer pathology, and of controls. Relative mRNA expression was determined by real-time PCR with neuron-specific enolase 2 and synaptophysin as housekeeping genes, and expression changes were evaluated by the ΔΔCt method. Two main findings are in concordance with earlier studies. First, all BS isoforms are drastically diminished in the cortex of patients with pure LBP that had presented clinically as DLB but not PD with dementia. Second, an important shift of the isoform expression ratio was observed in the temporal cortex of all LBD cases, and the minor isoforms, normally absent in the midbrain, were detected in the caudate nucleus of all DLB samples. Our results provide further evidence for the role of minor transcript variants in the development of complex diseases and provide new insights into the pathogenesis of LBDs that may be important for the understanding of molecular mechanisms involved in these complex diseases.

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Acknowledgments

The nervous tissue used in this research project has been provided by the Neurological Tissue Bank, University of Barcelona—Hospital Clínic de Barcelona, Barcelona, and the Institute of Neuropathology Brain Bank, L’Hospitalet, Spain. This work was supported by Spain’s Ministry of Health FIS grant CP09/00102.

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Authors and Affiliations

  1. Servicio de Anatomía Patológica, Hospital Universitario Germans Trias i Pujol, Ctra Canyet s/n, 08916, Badalona, Barcelona, Spain

    Katrin Beyer, Ana M. Munoz-Marmol, Carolina Sanz, Ruth Marginet-Flinch & Aurelio Ariza

  2. Institut de Neuropatologia, Servei d’Anatomia Patològica IDIBELL, Hospital Universitari de Bellvitge, Carrer Feixa Llarga s/n, 08907, Hospitalet de Llobregat, Barcelona, Spain

    Isidro Ferrer

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  1. Katrin Beyer
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  2. Ana M. Munoz-Marmol
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Correspondence to Katrin Beyer.

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Beyer, K., Munoz-Marmol, A.M., Sanz, C. et al. New brain-specific beta-synuclein isoforms show expression ratio changes in Lewy body diseases. Neurogenetics 13, 61–72 (2012). https://doi.org/10.1007/s10048-011-0311-8

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