Alzheimer's Disease Diagnostics Innovation and Translation to Clinical Practice in Central Europe

Informations projet

ADDIT-CE

N° de convention de subvention: 101087124

DOI

10.3030/101087124

Date de signature de la CE 10 Novembre 2022

Date de début 1 Janvier 2023

Date de fin 31 Decembre 2026

Financé au titre de

• Widening participation and spreading excellence

Coût total

€ 4 939 299,50

Contribution de l’UE

€ 4 939 299,50

Coordonné par

Masarykova univerzita
Czechia

Periodic Reporting for period 2 - ADDIT-CE (Alzheimer's Disease Diagnostics Innovation and Translation to Clinical Practice in Central Europe)

Période du rapport: 2024-04-01 au 2025-06-30

Résumé du contexte et des objectifs généraux du projet

More than 55 million people worldwide suffer from dementia. Alzheimer disease (AD) is the main cause of this fatal disorder, without any effective disease-modifying therapy. Early diagnosis and lifestyle modifications can significantly reduce care and treatment costs. There is no conceptual plan for implementing modern diagnostic methods in clinical practice in Czechia and Slovakia. The interaction between universities and the private sector in developing molecular diagnostic tools is fragmented and lacking. A limited number of talented students are invested in applied AD-focused research. The aim of ADDIT-CE is to interlink two ecosystems in Brno and Bratislava region, embracing the full quadruple helix of innovation-driving actors: excellent scientific teams from Masaryk University, and Slovak Academy of Sciences, collaborating with top biotech companies: Geneton, BioVendor, and MultiplexDX. Societal actors will be represented by organizations such as Slovak and Czech Alzheimer Societies, Memory Center, and Czech Brain Aging Study. The regional government will be involved via the Ministry of Health Slovak Republic and the South Moravian Innovation Centre. The joined ecosystems will unite R&I activities focusing on new diagnostic methods and their applications and further interlink academia and business spheres by creating a pilot industrial PhD program. ADDIT-CE will generate a joint cross-border strategy covering basic and applied research activities aiming at accelerating the development of new tools for preclinical AD diagnostics and lifestyle/pharmacological intervention monitoring. New cutting-edge technologies will be transferred into clinical practice. Results of ADDIT-CE will be used to develop the Slovak National Plan to Combat Dementia, to enrich the Czech National Plan for AD, and will be widely disseminated to end users and society. ADDIT-CE will join forces with the involved ecosystems to revolutionize diagnostic approaches in both countries.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Scientific efforts have focused on characterising tau fragments in the CSF, with particular emphasis on the MTBR region and ApoE structure, as well as developing a novel miRNA-seq protocol to identify Alzheimer’s biomarkers. In addition, we used several tau peptides identified in the CSF to generate antibodies recognising MTBR tau, with the aim of developing a tau diagnostic assay. The work also included harmonising protocols and sharing expertise between Czech and Slovak centres, along with standardising sample collection. We further enriched the screening with plasma ptau217 – a new biomarker reflecting tau pathology in the brain during both the preclinical and clinical stages of Alzheimer’s dementia.

The consortium has advanced the development of a preliminary Joint R&I Strategy, established biannual AD workshops to share current knowledge, and prepared guidelines to monitor technology development. We have also strengthened business–academia collaboration through hands-on training, the engagement of industrial PhD students, and a soft-skills workshop covering IPR, entrepreneurship, and science communication. In addition, fourteen scientific publications have been submitted to high-impact journals.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The progress and impact of the project's scientific work are currently very promising. We have launched multiple activities that may lead to the discovery of new tau, ApoE, and miRNA biomarkers. We have generated new monoclonal antibodies against MTBR tau, marking the initial step in developing a tau assay. Our miRNA protocol already demonstrates significantly better sensitivity than the industry standard. Structural insights into the tau protein have provided information about the complexity of its interaction with 14-3-3ζ proteins, leading us to propose several novel binding models. Cerebral organoids derived from iPSCs carrying AD-causative mutation have been collected and are now analyzed by high-throughput approaches to identify early pre-symptomatic biomarkers. Stem cell-based models are also being used to address the ApoE4-specific mechanisms of action, which could lead to a new drug development in the future. Our results have also linked the ApoE4 structure to its aggregation propensity.

We have continued genetic sequencing of 10 AD-related genes in patients and their relatives. For selected cases with unclear results, WES/WGS has been applied. We identified a pathogenic MAPT mutation (c.2341G>A, p.Gly781Arg) – the first reported in the Slovak population – with important epidemiological and clinical relevance. However, further research is essential to ensure that our innovations reach their full potential and achieve widespread impact.

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