Synucleinopathies are characterized by abnormal alpha-synuclein oligomerization and aggregation. Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are Lewy body diseases where aggregated alpha-synuclein deposits as Lewy bodies. Whereas PD is the most common movement disorder, DLB is the second most common cause of dementia after Alzheimer's disease (AD). DLB also shows an important neuropathological overlap with AD difficulting its clinical diagnosis. Additionally, PD, DLB and AD are characterised 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. However, they develop as a result of different primary molecular changes during the very first stages of the disease.
The research group’s main goal is to identify these different mechanisms to define different disease subgroups and, with the aim of disentangling this heterogeneity, its main objectives are:
- Molecular characterization of dementia with Lewy bodies with special focus on genetic variants, differential expression of alternative transcript variants and miRNAs.
- Identification of diagnostic biomarkers for dementia with Lewy bodies in different peripheral sources including blood, plasma, platelets and saliva.
- Establishment of cell and possibly also animal models suitable for testing of results.
- Development of diagnostic panels for the clinical diagnosis of dementias and Parkinson's disease.
The team’s research has a strong translational character, and so, their final aim is to translate research results from post-mortem brain tissue to peripheral tissues. So far, they have identified four biomarkers and have patented all of them. Two are specific for DLB subgroups, whereas the other two may serve as an early diagnostic marker of DLB.
Since neuropathological changes start up to 20 years before clinical symptoms of either PD or DLB become evident, they are currently extending their research to prodromic phases of Lewy body disorders.
Keywords: Lewy body diseases, dementia with Lewy bodies, Parkinson's disease, Alzheimer's disease, alpha-synuclein, alternative transcripts, platelets, blood biomarkers, saliva biomarkers.
Molecular characterisation 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.
Identification and characterisation 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.
Validación de biomarcadores líquidos y de imagen para el diagnóstico de la demencia con cuerpos de Lewy prodrómica
Co-PI: Katrin Beyer
Funding agency: Ministerio de Ciencia e Innovación
Agency code: PMP22/00100
Start date: 2023
End date: 2026
The role of platelets as biomarker reservoirs for dementia with Lewy bodies
PI: Katrin Beyer
Funding agency: Ministerio de Salud
Agency code: PI21/00833
Start date: 2022
End date: 2025
Blood miRNAs as diagnostic tool for dementia with Lewy bodies
PI: Katrin Beyer
Funding agency: Fondo Europeo de Desarrollo Regional (FEDER) - Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)
Agency code: 2021 PROD 00049
Start date: 2022
End date: 2024
Fernández-Ramos JA, De la Torre-Aguilar MJ, Quintáns B, Pérez-Navero JL, Beyer K, López-Laso E; Spanish Segawa Disease Research group. Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes. Parkinsonism Relat Disord. 2022 Jan;94:67-78. DOI: 10.1016/j.parkreldis.2021.11.014.
Katrin Beyer received Expertscape's Recognition as an Expert in Lewy bodies (placement by PubMed-based algorithms in the top 1% of scholars writing about Lewy Bodies over the past 10 years) in September 2021.
SNCA transcripts found in blood are candidate biomarkers for Lewy body dementia and Parkinson disease
In a new study published in the Journal of Molecular Science, the Genomics and Transcriptomics of Synucleinopathies Group, led by Dr Katrin Beyer, have got one step nearer to finding a reliable biomarker to differentiate between Lewy body dementia and Parkinson disease in the early stages, when symptoms are very similar. Correct diagnosis is extremely difficult, but essential for these patients as the wrong treatment can have very serious effects.
Three research groups at the IGTP have received three of the 21 grants in the 2019 call for CaixaImpulse, awarded by the "la Caixa" Foundation. The projects receiving the awards are led by Dr Katrin Beyer, Dr Francesc Borràs and Dr Alicia Martínez-Piñeiro and focus on improving the diagnostics for with Lewy body dementia; new non-invasive methods for monitoring renal dysfunction and new predictive markers for acute ischemic stroke respectively.