Objective Global increases in lifespan make the challenge to prevent and treat Alzheimer’s disease (AD) urgent. While the etiology of non-familial/sporadic AD is largely unknown, many AD patients have elevated stress hormone (glucocorticoid, GC) levels and recent animal studies show that high GC levels promote production of amyloidogenic peptides (key pathogenic players in AD) in association with memory deficits. Stress/GC are implicated in mood and cognitive disorders, and meta-analyses identify depression (often associated with cognitive deficits) as a risk for AD. This, and the fact that depression and AD involve similar limbic-cortical substrates, suggests shared spatio-temporal trajectories, with the two conditions representing early and late manifestations of increased amyloid beta (A-beta) levels. This proposal aims to i) define the spatio-temporal progression of the impact of stress on A-beta production based on morphochemical (immunochemical, gene expression, morphometric) mapping; and ii) identify the cellular targets and molecular mechanisms through which stress is pro-amyloidogenic (multiplex qPCR, Western blot, enzymatic activity assay). Two transgenic mice (arcAbeta and RiboTag mice) of different ages and sexes (women are more prone to AD and depression) will be used. Analysis of cellular events in genetically-marked (RiboTag) neuronal sub-populations adds innovative value. The applicant will apply his existing skills in structural and behavioral neurobiology, complemented by additional (primary neuronal culture, molecular and cellular neuroanatomy) and state-of-the-art methodologies (high-speed voltage-sensitive dye imaging and optogenetics), acquired at the host institute. Besides offering technical and generic skills, the host institute allows dialogue between basic and clinical researchers. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesbiochemistrybiomolecules Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2010-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Address Hofgartenstrasse 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Administrative Contact Silvia Juckoff Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data
