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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- engineering and technologymaterials engineeringcrystals
- engineering and technologyenvironmental biotechnologybioremediationbioreactors
- medical and health sciencesbasic medicineneurologydementiaalzheimer
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Programme(s)
Topic(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
53127 Bonn
Germany
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Participants (20)
2340 Beerse
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WC2R 2LS London
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53127 Bonn
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10117 Berlin
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WC1E 6BT London
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CB2 1TN Cambridge
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405 30 Goeteborg
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80686 Munchen
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20091 Bresso Milano
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
53127 Bonn
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
65205 Wiesbaden
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151 85 Sodertaelje
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RG21 4FA Basingstoke
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2500 Valby
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Participation ended
02200 Espoo
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4070 Basel
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94250 Gentilly
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75008 Paris
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Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.
80333 Munchen
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AL10 9SN Hatfield
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