CORDIS
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Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 - Sofia ref.: 115976

Inflammation and AD: modulating microglia function focussing on TREM2 and CD33 - Sofia ref.: 115976

Objective

Alzheimer’s disease (AD) is an age-related chronic neurodegenerative disease with four main pathological changes in the brain: amyloid plaques, fibrillary tau tangles, inflammation and neuronal loss. Phagocytes around amyloid plaques in late onset AD (LOAD) may be neurotoxic but have limited motility and phagocytic activity, suggesting a dysfunctional activation. These phagocytes express the innate immune receptor TREM2 and CD33. Variants of both genes have been linked to LOAD. The main objectives of PHAGO are to find means of modulating microglia/macrophage activation via TREM2, CD33 and related signalling pathways, and determine the effects of such modulation on microglia/macrophage function, amyloid-β and neurodegeneration, in order to find a treatment for AD. PHAGO will deliver well characterized tools and knowledge through which to manipulate AD risk and provide targets and markers ready to progress to drug development. PHAGO will realise this goal by comprehensively attacking the problem simultaneously at multiple levels, including the molecular structures of the receptors, receptor ligand interactions, ectodomain function in vitro and in vivo, characterisation of receptor processing, modification and signalling, receptor-regulated signalling pathways, gene expression and phagocyte function in cells and animals, comprehensive analysis of receptor knock-in and knock-out models crossed to two different animal models of AD, and identification of receptor-related biomarkers in AD patients. Innovative approaches of PHAGO will include identification of new AD-risk genes using a TREM2 co-expression network approach, brain imaging of AD patients with TREM2 and CD33 variants, and generation of patient iPSC-derived microglia/macrophages to comprehensively phenotype gene variants. The project will also generate tools, such as ligands, reporter cells and optimised assays, suitable for further development of treatments targeting TREM2 and/or CD33 in AD.
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Coordinator

UNIVERSITAETSKLINIKUM BONN

Address

Sigmund-Freud-Strasse 25
53127 Bonn

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 754 200

Participants (18)

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JANSSEN PHARMACEUTICA NV

Belgium

KING'S COLLEGE LONDON

United Kingdom

EU Contribution

€ 1 115 000

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV

Germany

EU Contribution

€ 1 027 500

CHARITE - UNIVERSITAETSMEDIZIN BERLIN

Germany

EU Contribution

€ 538 750

UNIVERSITY COLLEGE LONDON

United Kingdom

EU Contribution

€ 994 143,75

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

United Kingdom

EU Contribution

€ 1 052 500

GOETEBORGS UNIVERSITET

Sweden

EU Contribution

€ 372 156,25

FRAUNHOFER GESELLSCHAFT ZUR FOERDERUNG DER ANGEWANDTEN FORSCHUNG E.V.

Germany

EU Contribution

€ 500 000

AXXAM SPA

Italy

EU Contribution

€ 438 750

LIFE AND BRAIN GMBH

Germany

EU Contribution

€ 451 250

ABBVIE DEUTSCHLAND GMBH & CO KG

Germany

ASTRAZENECA AB

Sweden

Eli Lilly and Company Limited

United Kingdom

H. LUNDBECK AS

Denmark

ORION OYJ

Finland

F. HOFFMANN-LA ROCHE AG

Switzerland

SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT

France

ARTTIC

France

EU Contribution

€ 593 750

Project information

Grant agreement ID: 115976

Status

Ongoing project

  • Start date

    1 November 2016

  • End date

    31 October 2021

Funded under:

H2020-EU.3.1.7.

  • Overall budget:

    € 17 930 496

  • EU contribution

    € 8 838 000

Coordinated by:

UNIVERSITAETSKLINIKUM BONN

Germany