Project description DEENESFRITPL Role of tau strain diversity in the phenotypes of Alzheimer’s disease Dementia is a global challenge in our ageing world. Alzheimer’s disease (AD) is responsible for most dementia cases, yet no treatment is available. The EU-funded DIVE into AD project is searching for the determinants of AD clinical phenotypes via the analysis of pathological variants of the tau protein. It has been confirmed that tau deposition in the brain correlates with the hallmarks of AD neurodegeneration. Tau protein behaves like a prion and can spread from one neuron to another, and discrete tau strains generate distinct aggregates morphology and patterns of neuronal vulnerability. Therefore, the project's objective is to develop the technologies to identify tau strain fingerprints in different AD phenotypes. Show the project objective Hide the project objective Objective Dementia represents a major challenge for our ageing societies. The number of citizens suffering from dementia in the EU is expected to reach 19 millions by 2050. Alzheimer’s disease (AD) is responsible for the vast majority of dementia cases. However there is still not a single available treatment that modifies the course of disease. Therefore, the development of innovative approaches to better understand the pathophysiology and ultimately treat patients must be a priority. This project aims to understand the determinants of the diversity of AD clinical phenotypes through the deep analysis of pathological variants of the tau protein. As the accumulation of Aβ peptide has long been considered a causative event in AD, most therapeutic approaches have targeted Aβ metabolism, but unsuccessfully. Modern biomarkers, have confirmed that the brain deposition of tau pathology, the other hallmark of AD, correlates much better with human cognition and neurodegeneration. Recently, it was shown that tau behaves like a prion and can spread from one neuron to another. Moreover, tau strains or conformers seem to template native tau and propagate the pathological conformation with high fidelity. Discrete tau strains generate distinct aggregates morphology or patterns of neuronal vulnerability. I postulate that different strains of tau are responsible for the variability of AD and may determine the progression rate, gender differences or clinical expression. Therefore, my objective is to develop the technologies to identify tau strains signatures in distinct AD phenotypes. In particular, I plan to develop and optimize biosensor cell lines that sensitively detect tau strains from human brain samples and cerebrospinal fluid, and characterize respective repertoire of tau strains. Understanding AD heterogeneity would potentially increase our ability to take care of every individual patient. In addition, this work could lead to the development of biomarkers and novel targeted therapies. Fields of science natural sciencesbiological sciencesneurobiologyengineering and technologyelectrical engineering, electronic engineering, information engineeringelectronic engineeringsensorsbiosensorsmedical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesbasic medicinephysiologypathophysiologymedical and health sciencesbasic medicinepathology Keywords Alzheimer's disease tau prion propagation strains conformers personalized medicine Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITE DE GENEVE Net EU contribution € 190 207,68 Address RUE DU GENERAL DUFOUR 24 1211 Geneve Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Genève Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 190 207,68 Partners (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all Partner Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement. THE GENERAL HOSPITAL CORPORATION United States Net EU contribution € 0,00 Address FRUIT STREET 55 02114 Boston Ma See on map Activity type Other Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 88 632,96
