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Functional evaluation of newly identified deregulated genes in Alzheimer's Disease patients using neuronal cultures and mouse model of the Disease, and possible contributions to Prion Disease

AdAPtoGENE

Start Date
End Date
Total Funding
€ 168 896
Funding Programme
European Countries Involved

Neurodegenerative diseases (NDs) are the neurological disorders which will affect a significantly growing number of people in the context of the aging of the EU's population and worldwide. NDs thus constitute a priority for action. Alzheimer’s Disease (AD) is the most common form of dementia and ND, and a major social and health problem. Preliminary data from the host laboratory identified a subset of significantly deregulated genes in brain tissue of AD affected individuals. We here propose to test how and to which extent activation or suppression of these genes confers susceptibility to AD. We propose two approaches: the first in vitro, to analyze how the modification of the expression of these genes influences neuronal cultures survival and plasticity in the old stage, and the susceptibility of neurons to Amyloid beta toxicity. Then, the most promising genes will be further selected for an in vivo screening in transgenic mouse model of AD, to elucidate whether the alteration of the expression of these genes may modify and hopefully counteract the signs of AD in vivo. Additionally, as recent advances in Prion diseases, another family of NDs affecting humans and animals, and AD research suggest that AD and Prion diseases converge in many pathogenic aspects, and may even be amenable to similar therapeutic principles, we propose to analyze the contribution of these genes also in Prion disease cellular models, and whether alteration of Prion biology may in turn contribute to AD pathology. This fellowship will give important information on aberrant genetic, cellular and molecular mechanisms responsible for NDs such as AD, and will open direct leads for early diagnosis and prevention. The fellow will acquire a more complete and diversified scientific knowledge and technical preparation through a multi-disciplinary approach, and will be trained to become an expert researcher towards an independent research career in the field of neuroscience, in particular of NDs and AD

Project partners

Agencia Estatal Consejo Superior Deinvestigaciones Cientificas

 
Acknowledgement
Alzheimer Europe's database on research projects was developed as part of the 2020 Work Plan which received funding under an operating grant from the European Union’s Health Programme (2014–2020).