Genomics and transcriptomics of synucleinopathies

Katrin Beyer

Synucleinopathies encompass three diseases that are characterized by abnormal  α-synuclein oligomerization and deposition in specific brain areas. In multiple system atrophy, α-synuclein aggregates to form glial cytoplasmic inclusions and in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) to form Lewy bodies. PD is the most common movement disorder and DLB the second most common cause of dementia after Alzheimer's disease (AD), and both are also referred to as Lewy body diseases.

Our research focuses on the molecular characterization of Lewy body diseases, including both genomic and transcriptomic research. In this context we have established expression profiles of different transcript variants from genes primarily involved in disease development in post-mortem brain samples. An important highlight in our research has been the characterization of the first molecular subgroup of DLB, published in 2010 in Brain. This finding has opened new avenues in the research of Lewy body diseases and revealed the possible existence of a new therapeutic target for at least one specific subgroup of DLB patients.

Neurodegenerative disorders are characterized by a high grade of heterogeneity, so that PD and DLB are only umbrella terms for groups of diseases showing similar pathological and clinical features, but that have developed as a result of different primary molecular changes. Our goal is to identify these different mechanisms for defining different disease subgroups. Only the identification of these subgroups will permit the establishment of disease markers and specific therapies getting a step closer to the implementation of personalized medicine.

So, our final aim is to translate research results from post-mortem brain tissue to peripheral tissues and to discover peripheral disease markers through liquid biopsy. So far we have identified four biomarkers; two of them are specific for DLB subgroups, whereas the other two may serve as an early diagnostic marker of DLB. These findings have given rise to four patents. One of these patents, filed in 2015, has been extended worldwide (WO2011/104023), and the latest one has been requested in July, 2018.

Selected Publications K Beyer

Publications K Beyer

Patents K Beyer

Líneas de investigación

Line 1: Molecular characterization of Lewy body diseases

Within this research line we focus on the following aspects:  (1) search for genetic variation, comprising the characterization of polynucleotide sequences, such as INDELs, microsatellites and polynucleotide stretches within promoter and intronic regions; (2) expression analysis of genes involved in the pathogenesis of Lewy body disorders, and of alternative splicing including both in-frame splicing and variable promoter usage; (3) analysis of miRNAs expression changes in brain and blood; (4) 3'UTR variation analysis of genes involved in the pathogenesis of Lewy body disorders; (5) functional and integrated analyses to establish which promoter variants (polynucleotides and/or microsatellites) co-regulate transcriptional activity, which intronic variants co-regulate alternative splicing and which 3'UTR variants change miRNA interactions altering posttranscriptional regulation of gene expression.

Line 2: Identification of diagnostic biomarkers for dementia with Lewy bodies

Within this research line, we aim to translate the findings made in post-mortem brain samples to blood and saliva to identify peripheral diagnostic biomarkers for Lewy body disease to be used in the clinical practice. Our latest data provide a solid basis for the development of genetic biomarkers for the early identification of patients suffering from DLB and to classify them into specific molecular subtypes. One of the biomarkers correlates with the development of Lewy pathology in the brain and may be useful to monitor the success of possible alpha-synuclein antiaggregatory therapies.

Line 3: Establishment of cell and animal models suitable for testing of results

Since there has not been the desired success in the application of transgenic mice models in therapy testing for neurodegenerative disorders, we are interested in the implementation of a natural animal model. This animal is the Octodon degus, a small diurnal rodent native to South America that can spontaneously develop cognitive decline with concomitant phosphor-tau, alpha synuclein, beta-amyloid pathology and neuroinflammation in brain. Consequently, the Octodon degus is a suitable model for use in the search to find the cause and disease-modifying treatments for AD as well as DLB. We have established a tight collaboration with the group led by Dr Patricia Cogram in the University of Chile and have started neuropathologic studies of the animal.

Current Research projects

mRNA expression profiles of glucocerebrosidase and its regulador genes in brain and blood: Identification of biological signatures for Lewy body dementia

Code: PI15/00216
Principlal Investigator: Katrin Beyer                                                                                               
Start Date: 2016
End Date: 2019

Identification of specific biosignatures from plasma samples for the differential diagnosis of dementia with Lewy bodies

Code: 201405.10
Principlal Investigator: Katrin Beyer                                                                                               
Start Date: 2015
End Date: 2018


Més informació


Katrin Beyer

(+34) 93 497 8853 ext 3959