The work will be carried out within the laboratory of neurodegenerative diseases (UMR9199) in the MIRCen center in Fontenay aux Roses. This laboratory is dedicated to the study of the mechanisms of degeneration, brain imaging and therapeutic drug strategies for neurodegenerative diseases, in particular Alzheimer's disease.
Alzheimer's disease is linked to cerebral accumulation of aggregated amyloid-β (Aβ) peptides that initiate a pathological cascade leading to tau protein aggregation and spread as well as synaptic alterations. Microglia are now established as key regulators of Alzheimer's disease, but the nature of the interactions between microglial changes and Alzheimer's disease pathophysiology is still unclear. These links have been mainly established in rodent models whereas microglial reactions are different between rodents and primates. The host laboratory induced Aβ/tau pathologies as well as cognitive alterations in a primate (Microcebus murinus). The working hypothesis of this thesis is that the evaluation of microglial changes in response to induced Alzheimer's disease will provide invaluable new insights with strong translational potential towards future therapeutic strategies against Alzheimer's disease. The aims of the thesis are to. 1. Phenotype microglia during aging and Alzheimer's pathology induced in a primate, including by transcriptomic approaches. 2. To assess the impact of a treatment that blocks microglia proliferation and changes the microglial inflammatory profile to an anti-inflammatory phenotype. The ability to limit microglial activation will allow assessment of the relationships between changes in microglia and the pathophysiology of Alzheimer's disease. Overall, this project will provide a better understanding of the pathophysiology of Alzheimer's disease.Web site for additional job details
https: // emploi.cnrs.fr/Offres/Doctorant/UMR9199-MARDHE-001/Default.aspxRequired Research Experiences
Pharmacological sciences: Master Degree or equivalent
Engineering: Master Degree or equivalent
Technology: Master Degree or equivalent
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