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URBACH-ALZ

Hyper-emotionality after neurodegenerative loss of inhibition of the amygdala

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

URBACH-ALZ project word cloud

Explore the words cloud of the URBACH-ALZ project. It provides you a very rough idea of what is the project "URBACH-ALZ" about.

profiles settlers decrease basis central tests causal deeper disorders lab causally translational human insecurely host individuals damage uniquely chemogenetic patients fear projections personality town found mri model function ot collaborators cape onto plan worldwide uwd disease cea center attachment mutation neurobiological dutch genetic firm blood occurring hyper ad south levels signaling adding urbach rare gained opto reported gt bilateral bla 400 animal alzheimer decreased group basolateral hypothesis treat inhibitory africa lausanne behavioral handful give construct anxiety clinical anc functional cerebrospinal university spread caused special hypothesize stronger wie amygdala relation fluid oxytocin chemogenetically correlating neurodegeneration attached animals anatomical causes started multidisciplinary

Project "URBACH-ALZ" data sheet

The following table provides information about the project.

Coordinator	FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Organization address address: VIA MOREGO 30 city: GENOVA postcode: 16163 website: www.iit.it contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Italy [IT]
Total cost	173˙634 €
EC max contribution	173˙634 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2015
Funding Scheme	MSCA-IF-EF-ST
Starting year	2017
Duration (year-month-day)	from 2017-01-01 to 2018-12-31

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA	IT (GENOVA)	coordinator	42˙069.00
2	CENTRE HOSPITALIER UNIVERSITAIRE VAUDOIS	CH (LAUSANNE)	participant	131˙564.00

Map

Project 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. '

Publications

List of publications.
year	authors and title	journal	last update
2018	David Terburg, Diego Scheggia, Rodrigo Triana del Rio, Floris Klumpers, Alexandru Cristian Ciobanu, Barak Morgan, Estrella R. Montoya, Peter A. Bos, Gion Giobellina, Erwin H. van den Burg, Beatrice de Gelder, Dan J. Stein, Ron Stoop, Jack van Honk The Basolateral Amygdala Is Essential for Rapid Escape: A Human and Rodent Study published pages: 723-735.e16, ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.09.028	Cell 175/3	2019-08-30

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