Objective "I propose to test how hyper-anxiety in Alzheimer's disease (AD) patients is caused by neurodegeneration in the amygdala, our ""center of fear"", by comparing with a unique group of Urbach Wiethe disease (UWD) patients with bilateral neurodegeneration of the amygdala (BLA) for which I also construct an animal model. UWD is caused by a very rare genetic mutation occurring in only a handful of individuals worldwide. My host in Lausanne has gained access, however, to a uniquely large group of UWD patients in South-Africa (>40) where the mutation has spread for 400 years in Dutch settlers. Our collaborators at Cape Town University have found, in anatomical & functional MRI and special behavioral tests, how specific loss of inhibitory projections from the basolateral (BLA) onto the central part of the amygdala (CeA) causes hyper-anxiety in UWD. Based upon recently reported BLA neurodegeneration in AD patients, I hypothesize a crucial BLA role in hyper-anxiety of AD patients. I plan to test this in AD patients with clinical collaborators in Lausanne and, to test this hypothesis causally, I have started to opto,- anc chemogenetically decrease BLA function in an animal model.In addition, in Lausanne a stronger hyper-anxiety was observed in AD patients with insecurely attached personality profiles. As my host lab has established an inhibitory role of oxytocin (OT) in the CeA, I hypothesize a decreased OT signaling in CeA of these patients, adding to the anxiety already caused by the BLA loss. I plan to test this both in AD and UWD patients by correlating attachment profiles with OT levels (in blood & cerebrospinal fluid) and anxiety levels & BLA damage (MRI). I will use opto&chemogenetic targeting of OT signaling in animals for a causal relation. This multidisciplinary and translational approach can give a deeper understanding of the role of the amygdala in hyper-anxiety in human patients, and provide a firm neurobiological basis for applying OT to treat anxiety disorders." Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicinepharmacology and pharmacydrug discoverymedical and health sciencesbasic medicineneurologydementiaalzheimermedical and health sciencesclinical medicinepsychiatryposttraumatic stress disordermedical and health sciencesclinical medicinepsychiatryanxiety disorders 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-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2015 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Net EU contribution € 42 069,30 Address VIA MOREGO 30 16163 Genova Italy See on map Region Nord-Ovest Liguria Genova Activity type Research Organisations 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 € 42 069,30 Participants (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS Participation ended Switzerland Net EU contribution € 131 564,70 Address RUE DU BUGNON 21 1011 Lausanne See on map Region Schweiz/Suisse/Svizzera Région lémanique Vaud Activity type Public bodies (excluding Research Organisations and Secondary or Higher 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 € 131 564,70