Objectif Alzheimer’s disease (AD) affects worldwide ~50 million people. Preclinical research relies mainly on transgenic mouse models overexpressing mutant human proteins that are altered in <5% of AD cases (e.g. β-amyloid and tau), however, despite prominent protein aggregates, they fail to show the dramatic neurodegeneration and cognitive decline of patients, indicating that plaques and tangles may not be the only requirement for AD. Age is the most determining factor in AD, but is poorly represented in current AD models.Generating bona fide mouse models for various human DNA repair syndromes we have disclosed a very strong connection between DNA damage, repair and aging including dramatic neurodegeneration. Within the context of ERC-DamAge we discovered striking parallels in neurodegeneration, progressive cognitive decline and genome-wide expression profiles of repair-deficient Ercc1Δ/- mice and human AD. The similarities in expression profiles are an order of magnitude higher than current AD mouse models. We discovered that nutritional interventions can spectacularly delay neurodegeneration, opening realistic perspectives for combating AD and other neurodegenerative disorders. The primary goal of this application is to complete the characterization of the mouse mutants as a valid model for AD by a detailed quantitative comparison of all RNA classes of relevant brain compartments of Ercc1Δ/- mutants and AD patients. This not only provides the final PoC, but also an unparalleled resource for pathway analysis, target identification and biomarkers for monitoring disease progression and effects of any intervention. This application will be instrumental to facilitate transition to a valid AD model for pharmaceutical companies enabling development of effective medication for prevention and/or therapy. This proposal addresses a huge unmet medical need worldwide, which seriously affects QoL, challenges health care systems, and offers unprecedented socio-economical opportunities. Champ scientifique natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-PoC-2014 - ERC Proof of Concept Grant Appel à propositions ERC-2014-PoC Voir d’autres projets de cet appel Régime de financement ERC-POC - Proof of Concept Grant Institution d’accueil ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Contribution nette de l'UE € 150 000,00 Adresse DR MOLEWATERPLEIN 40 3015 GD Rotterdam Pays-Bas Voir sur la carte Région West-Nederland Zuid-Holland Groot-Rijnmond Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 150 000,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM Pays-Bas Contribution nette de l'UE € 150 000,00 Adresse DR MOLEWATERPLEIN 40 3015 GD Rotterdam Voir sur la carte Région West-Nederland Zuid-Holland Groot-Rijnmond Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 150 000,00