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

Total Cost €


EC-Contrib. €






 PHAGO project word cloud

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

load    treatments    comprehensively    express    limited    linked    microglia    neuronal    pathological    onset    function    tangles    phagocytic    levels    signalling    phago    manipulate    patient    attacking    inflammation    phagocyte    generate    structures    progress    drug    chronic    imaging    variants    models    motility    activation    markers    macrophage    ligands    phenotype    macrophages    molecular    suggesting    alzheimer    animal    crossed    knock    network    identification    expression    innovative    fibrillary    cd33    innate    disease    generation    realise    biomarkers    ready    simultaneously    neurotoxic    amyloid    modulation    cells    treatment    co    plaques    age    vivo    assays    animals    ad    risk    neurodegeneration    genes    immune    patients    reporter    phagocytes    suitable    characterisation    interactions    ectodomain    modulating    receptors    beta    tau    gene    vitro    ligand    multiple    ipsc    trem2    tools    modification    regulated    brain    dysfunctional    neurodegenerative    receptor   

Project "PHAGO" data sheet

The following table provides information about the project.


Organization address
city: BONN
postcode: 53127

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 Germany [DE]
 Project website
 Total cost 18˙088˙176 €
 EC max contribution 8˙838˙000 € (49%)
 Programme 1. H2020-EU.3.1.7. (Innovative Medicines Initiative 2 (IMI2))
 Code Call H2020-JTI-IMI2-2015-05-two-stage
 Funding Scheme IMI2-RIA
 Starting year 2016
 Duration (year-month-day) from 2016-11-01   to  2021-10-31


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITATSKLINIKUM BONN DE (BONN) coordinator 1˙754˙200.00
2    KING'S COLLEGE LONDON UK (LONDON) participant 1˙115˙000.00
5    UNIVERSITY COLLEGE LONDON UK (LONDON) participant 994˙143.00
6    ARTTIC FR (PARIS) participant 593˙750.00
9    LIFE AND BRAIN GMBH DE (BONN) participant 451˙250.00
10    AXXAM SPA IT (BRESSO MILANO) participant 438˙750.00
11    GOETEBORGS UNIVERSITET SE (GOETEBORG) participant 372˙156.00
13    ASTRAZENECA AB SE (SODERTAELJE) participant 0.00
14    EISAI LIMITED UK (HATFIELD) participant 0.00
15    Eli Lilly and Company Limited UK (Basingstoke) participant 0.00
16    F. HOFFMANN-LA ROCHE AG CH (BASEL) participant 0.00
17    H. LUNDBECK AS DK (VALBY) participant 0.00
19    ORION OYJ FI (ESPOO) participant 0.00
20    SANOFI-AVENTIS RECHERCHE & DEVELOPPEMENT FR (Chilly Mazarin) participant 0.00


 Project 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.


List of deliverables.
Knowledge of possible disease mechanisms and targets Documents, reports 2020-04-08 21:13:17
Crystal structure of CD33 generated to ~3 Ã… and refined to ~2 Ã… Documents, reports 2020-04-08 21:13:17
Determination of the cleavage site Documents, reports 2020-04-08 21:13:16
A comprehensive roadmap for data and knowledge management for the PHAGO consortium, collection of pre-existing ethical documents Documents, reports 2020-04-08 21:13:17
Press release containing a common part and a part that can be personalised by every partner Websites, patent fillings, videos etc. 2020-04-08 21:13:16
Launch of website, Twitter and other dissemination activities Websites, patent fillings, videos etc. 2020-04-08 21:13:17
Completion of the analysis of changes in the glycosylation of TREM2 ectodomains in the presence of R47H variants Documents, reports 2020-04-08 21:13:17
CD33 receptor ligands characterization in human primary monocytes Documents, reports 2020-04-08 21:13:17
Providing existing RNAseq signatures and cytokine/chemokine signatures of microglia from tg4510 (tau) mice at various time points Demonstrators, pilots, prototypes 2020-04-08 21:13:17

Take a look to the deliverables list in detail:  detailed list of PHAGO deliverables.


year authors and title journal last update
List of publications.
2019 Samira Parhizkar, Thomas Arzberger, Matthias Brendel, Gernot Kleinberger, Maximilian Deussing, Carola Focke, Brigitte Nuscher, Monica Xiong, Alireza Ghasemigharagoz, Natalie Katzmarski, Susanne Krasemann, Stefan F. Lichtenthaler, Stephan A. Müller, Alessio Colombo, Laura Sebastian Monasor, Sabina Tahirovic, Jochen Herms, Michael Willem, Nadine Pettkus, Oleg Butovsky, Peter Bartenstein, Dieter Edb
Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
published pages: 191-204, ISSN: 1097-6256, DOI: 10.1038/s41593-018-0296-9
Nature Neuroscience 22/2 2020-04-08
2017 Johannes Jungverdorben, Andreas Till, Oliver Brüstle
Induced pluripotent stem cell-based modeling of neurodegenerative diseases: a focus on autophagy
published pages: 705-718, ISSN: 0946-2716, DOI: 10.1007/s00109-017-1533-5
Journal of Molecular Medicine 95/7 2020-04-08
2019 Meliha Karsak, Konstantin Glebov, Marina Scheffold, Thomas Bajaj, Amit Kawalia, Ilker Karaca, Sebastian Rading, Johannes Kornhuber, Oliver Peters, Monica Diez‐Fairen, Lutz Frölich, Michael Hüll, Jens Wiltfang, Martin Scherer, Steffi Riedel‐Heller, Anja Schneider, Michael T. Heneka, Klaus Fliessbach, Ahmed Sharaf, Holger Thiele, Martina Lennarz, Frank Jessen, Wolfgang Maier, Christian Kubisch
A rare heterozygous TREM2 coding variant identified in familial clustering of dementia affects an intrinsically disordered protein region and function of TREM2
published pages: , ISSN: 1059-7794, DOI: 10.1002/humu.23904
Human Mutation 2020-04-08
2019 Antonio Boza-Serrano, Rocío Ruiz, Raquel Sanchez-Varo, Juan García-Revilla, Yiyi Yang, Itzia Jimenez-Ferrer, Agnes Paulus, Malin Wennström, Anna Vilalta, David Allendorf, Jose Carlos Davila, John Stegmayr, Sebastian Jiménez, Maria A. Roca-Ceballos, Victoria Navarro-Garrido, Maria Swanberg, Christine L. Hsieh, Luis M. Real, Elisabet Englund, Sara Linse, Hakon Leffler, Ulf J. Nilsson, Guy C. Bro
Galectin-3, a novel endogenous TREM2 ligand, detrimentally regulates inflammatory response in Alzheimer’s disease
published pages: 251-273, ISSN: 0001-6322, DOI: 10.1007/s00401-019-02013-z
Acta Neuropathologica 138/2 2020-04-08
2019 Luke A. Miles, Stefan J. Hermans, Gabriela A.N. Crespi, Jonathan H. Gooi, Larissa Doughty, Tracy L. Nero, Jasmina Markulić, Andreas Ebneth, Berthold Wroblowski, Daniel Oehlrich, Andrés A. Trabanco, Marie-Laure Rives, Ines Royaux, Nancy C. Hancock, Michael W. Parker
Small Molecule Binding to Alzheimer Risk Factor CD33 Promotes Aβ Phagocytosis
published pages: 110-118, ISSN: 2589-0042, DOI: 10.1016/j.isci.2019.07.023
iScience 19 2020-04-08
2019 Guy C. Brown
The endotoxin hypothesis of neurodegeneration
published pages: , ISSN: 1742-2094, DOI: 10.1186/s12974-019-1564-7
Journal of Neuroinflammation 16/1 2020-04-08
2018 Bettina Linnartz‐Gerlach, Liviu‐Gabriel Bodea, Christine Klaus, Aurélien Ginolhac, Rashi Halder, Lasse Sinkkonen, Jochen Walter, Marco Colonna, Harald Neumann
TREM2 triggers microglial density and age‐related neuronal loss
published pages: , ISSN: 0894-1491, DOI: 10.1002/glia.23563
Glia 2020-04-08
2018 A.E. M. Phillips, C. Villegas Llerena, T.M. Piers, K. Cosker, J. Hardy and J. M. Pocock
Loss of Function of TREM2 Results in Cytoskeletal Malfunction in Microglia
published pages: , ISSN: 2379-7150, DOI:
Journal of Neurology and Neurobiology Voulme 4 Issue 3 2020-04-08
2017 Peter Thornton, Jean Sevalle, Michael J Deery, Graham Fraser, Ye Zhou, Sara Ståhl, Elske H Franssen, Roger B Dodd, Seema Qamar, Beatriz Gomez Perez‐Nievas, Louise SC Nicol, Susanna Eketjäll, Jefferson Revell, Clare Jones, Andrew Billinton, Peter H St George‐Hyslop, Iain Chessell, Damian C Crowther
TREM2 shedding by cleavage at the H157‐S158 bond is accelerated for the Alzheimer\'s disease‐associated H157Y variant
published pages: 1366-1378, ISSN: 1757-4676, DOI: 10.15252/emmm.201707673
EMBO Molecular Medicine 9/10 2020-04-08
2017 Kai Schlepckow, Gernot Kleinberger, Akio Fukumori, Regina Feederle, Stefan F Lichtenthaler, Harald Steiner, Christian Haass
An Alzheimer‐associated TREM2 variant occurs at the ADAM cleavage site and affects shedding and phagocytic function
published pages: 1356-1365, ISSN: 1757-4676, DOI: 10.15252/emmm.201707672
EMBO Molecular Medicine 9/10 2020-04-08
2018 Guillermo Carbajosa, Karim Malki, Nathan Lawless, Hong Wang, John W. Ryder, Eva Wozniak, Kristie Wood, Charles A. Mein, Richard J.B. Dobson, David A. Collier, Michael J. O\'Neill, Angela K. Hodges, Stephen J. Newhouse
Loss of Trem2 in microglia leads to widespread disruption of cell coexpression networks in mouse brain
published pages: 151-166, ISSN: 0197-4580, DOI: 10.1016/j.neurobiolaging.2018.04.019
Neurobiology of Aging 69 2020-04-08
2018 Alejandro Carrillo-Jimenez, Mar Puigdellívol, Anna Vilalta, Jose Luis Venero, Guy Charles Brown, Peter StGeorge-Hyslop, Miguel Angel Burguillos
Effective Knockdown of Gene Expression in Primary Microglia With siRNA and Magnetic Nanoparticles Without Cell Death or Inflammation
published pages: , ISSN: 1662-5102, DOI: 10.3389/fncel.2018.00313
Frontiers in Cellular Neuroscience 12 2020-04-08
2018 Xianyuan Xiang, Thomas M. Piers, Benedikt Wefers, Kaichuan Zhu, Anna Mallach, Bettina Brunner, Gernot Kleinberger, Wilbur Song, Marco Colonna, Jochen Herms, Wolfgang Wurst, Jennifer M. Pocock, Christian Haass
The Trem2 R47H Alzheimer’s risk variant impairs splicing and reduces Trem2 mRNA and protein in mice but not in humans
published pages: , ISSN: 1750-1326, DOI: 10.1186/s13024-018-0280-6
Molecular Neurodegeneration 13/1 2020-04-08
2018 Pablo Garcia-Reitboeck, Alexandra Phillips, Thomas M. Piers, Claudio Villegas-Llerena, Matt Butler, Anna Mallach, Celia Rodrigues, Charles E. Arber, Amanda Heslegrave, Henrik Zetterberg, Harald Neumann, Stephen Neame, Henry Houlden, John Hardy, Jennifer M. Pocock
Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis
published pages: 2300-2311, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.07.094
Cell Reports 24/9 2020-04-08

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