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Inflammation and AD: modulating microglia function focussing on TREM2 and CD33


Start Date
End Date
Total Funding
€ 18 088 176
Funding Programme

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.

Project partners

Abbvie Deutschland Gmbh & Co Kg

Deutsches Zentrum Fur Neurodegenerative Erkrankungen Ev

The Chancellor Masters And Scholarsof The University Of Cambridge

Fraunhofer Gesellschaft Zur Foerderung Der Angewandten Forschung E.V.

Astrazeneca Ab

F. Hoffmann-La Roche Ag

Orion Oyj

Eisai Limited

Life And Brain Gmbh

H. Lundbeck As

Charite - Universitaetsmedizin Berlin


Sanofi-Aventis Recherche & Developpement

Axxam Spa

University College London

Eli Lilly And Company Limited

Goeteborgs Universitet

Janssen Pharmaceutica Nv

King'S College London

Universitatsklinikum Bonn

Alzheimer Europe's database on research projects was developed as part of the 2020 Work Plan which received funding under an operating grant from the European Union’s Health Programme (2014–2020).