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Name ADAPTED
Long Name Alzheimer's disease apolipoprotein pathology for treatment elucidation and development
Description Alzheimer's disease apolipoprotein pathology for treatment elucidation and development. The ADAPTED project aims to boost the development of new medicines by investigating an area of AD research which has previously received little attention – the APOE gene. The APOE gene is a well-known risk factor for developing the disease, but precisely how this gene contributes to the risk of developing AD is not known. People who carry the APOE4 version of the gene have a considerably higher risk of developing AD. They also tend to develop the disease much earlier in life. However, the reasons for this are not well understood and therefore APOE has largely been ignored in the quest to find treatments for AD. By bringing together leading experts in a range of state-of-the-art technologies, including three research-intensive small and medium-sized enterprises (SMEs), ADAPTED hopes to gain better insights into the causes of AD, something that will in turn lead to better treatments for patients.
Objectives 1. Clarify the role of APOE as a risk factor in the development of AD. 2. Identify promising entry points (targets) for the treatment of AD. 3. Generate and validate selected high value APOE-related model systems. 4. Uncover the basic scientific evidence required to progress the development of a stratified approach.
Website https://www.imi-adapted.eu/
Start date 01-10-2016
End date 30-09-2020
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Name Projects Type of institution Country  
Janssen Pharmaceutica NV EPAD ADAPTED AMYPAD IMPRiND EQIPD NEURONET EMIF IM2PACT PHAGO PRISM RADAR-CNS RADAR-AD ROADMAP IDEA-FAST Pharma-Cog EPND EFPIA Belgium
Biogen Idec Limited EPAD RADAR-CNS ROADMAP ADAPTED IDEA-FAST EFPIA United Kingdom
Klinikum Der Universitaet Zu Koeln EPAD AMYPAD MOPEAD ADAPTED Academia Germany
Erasmus Universitair Medisch Centrum Rotterdam PRISM ADAPTED AETIONOMY EMIF ROADMAP EPAD IDEA-FAST Academia Netherlands
Universitaetsklinikum Bonn AETIONOMY ADAPTED PHAGO Academia Germany
Abbvie Deutschland GMBH & Co Kg ADAPTED PHAGO EFPIA Germany
Agencia Estatal Consejo Superior De Investigaciones Cientificas ADAPTED Academia Spain
Fundació ACE ADAPTED MOPEAD Academia Spain
Universiteit Leiden ADAPTED Academia Netherlands
Caebi Bioinformatica SL ADAPTED SME Spain
DC Biosciences LTD ADAPTED SME United Kingdom
Mimetas BV ADAPTED IM2PACT PD-MitoQUANT SME Netherlands
Modus Research And Innovation Ltd ADAPTED MOPEAD SME United Kingdom
WP number Description Project  
WP1 Consortium management and governance ADAPTED
WP2 APOE Models ADAPTED
WP3 APOE and Neurodegeneration ADAPTED
WP4 ApoE and AD risk factors ADAPTED
WP5 Data and Knowledge Management ADAPTED
Deliverable number Title Project Submission date Link Keywords  
D4.2 Definition of cognitive composite scores to evaluate rate of disease progression based on cognitive function decline in ADAPTED cohorts ADAPTED 22-09-2017 https://ec.europa.eu/research/participants/documents/downloadPublic?documentIds=080166e5b89c4429&appId=PPGMS
Title First author last name Year Project Link Keywords  
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease Sims 2017 ADAPTED https://doi.org/10.1038/ng.3916 Clinical research paper, GWAS, genetic risk factor, inflammation, Alzheimer's disease, TREM2
A perfused human blood–brain barrier on-a-chip for high-throughput assessment of barrier function and antibody transport Wevers 2018 ADAPTED https://doi.org/10.1186/s12987-018-0108-3 Basic science research paper, Blood–brain barrier, microfluidics, organ-on-a-chip, antibody transcytosis
Blood-derived integration-free iPS cell line UKBi011-A from a diagnosed male Alzheimer's disease patient with APOE ɛ4/ɛ4 genotype Peitz 2018 ADAPTED https://doi.org/10.1016/j.scr.2018.04.011 Basic science research paper, clinical research, iPSC, Alzheimer's disease, ApoE
Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies van der Lee 2018 ADAPTED https://doi.org/10.1016/j.jalz.2017.11.012 Clinical research paper, cognitive function, General cognitive ability, Alzheimer's disease, dementia, metabolites, metabolomics, NMR, lifestyle factors
CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE ε4 carriers Ahmad 2020 ADAPTED https://doi.org/10.1038/s41598-020-65038-5 Clinical research paper, ApoE, Alzheimer's disease, biomarker, GWAS
PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment Kleineidam 2020 ADAPTED https://doi.org/10.1007/s00401-020-02138-6 Clinical research paper, MCI, alzheimer's disease, GWAS, cognitive decline
Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer’s disease Ahmad 2020 ADAPTED https://doi.org/10.1186/s13195-020-00680-9 Lysophosphatidic acids, Pro-inflammatory phospholipids, Signaling lipids, CSF biomarkers, Alzheimer’s disease, MCI
Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer’s disease etiopathogenesis Madrid 2021 ADAPTED https://doi.org/10.18632/aging.202950 Alzheimer’s disease, APOE, integrative analysis, biomarkers
Generation of a set of isogenic iPSC lines carrying all APOE genetic variants (Ɛ2/Ɛ3/Ɛ4) and knock-out for the study of APOE biology in health and disease Schmid 2021 ADAPTED https://doi.org/10.1016/j.scr.2021.102180 antibody, cell, antibodies, genotype, cells, alzheimer, sox, disease, rna, apoe
Title Description Type Project  
Omics data from iPSC cells, humanised ApoE mouse models

ADAPTED has collected RNA from iPSC-generated neurons, microglia, patient-derived monocytes and humanised APOE mouse models, and will collect RNA from iPSC-generated astrocytes and macrophages. Methylome analysis has been completed for patient-derived monocytes. Proteomics analysis has been completed for iPSC-derived astrocytes, iPSC-derived macrophages, iPSC-derived microglia, humanised APOE mouse models. Metabolomics analysis has been completed for iPSC-derived neurons and astrocytes. Datasets will be available after the end of the project embargo period. For more information, please visit:

https://www.imi-adapted.eu/single-post/2020/09/29/cells-data-and-publications-the-legacy-of-adapted

dataset-non-clinical-adapted-1 ADAPTED
Omics data from CSF/plasma from MCI patients

ADAPTED has generated proteomics and metabolomics datasets from CSF and plasma samples from MCI patients. Datasets will be available after the end of the project embargo period. For more information, please visit:

https://www.imi-adapted.eu/single-post/2020/09/29/cells-data-and-publications-the-legacy-of-adapted

dataset-clinical-adapted-7 ADAPTED
Biosamples from people with AD, MCI, or healthy individuals

Sample collections obtained from 1,193 individuals (blood, DNA, plasma, serum, saliva and CSF) have been generated by Fundació ACE and have been registered in the Spanish national registry of biobanks (Instituto de Salud Carlos III Reg. num. C.0000299). The repository is accessible for research purposes to anyone interested. Sample access requests are reviewed and negotiated individually, regulated by Spanish legislation (Royal Decree 1716/2011; Act 14/2007) . A Materials and Data transfer agreement (MDTA) is signed between Fundació ACE and research groups requesting access to this collection. For more information please visit:

https://biobancos.isciii.es/ListadoColecciones.aspx

biological-samples-clinical-adapted-1 ADAPTED
iPSC-derived cell models of ApoE risk alleles

To model the cellular effects of ApoE genotypes in vitro, ADAPTED has used genome editing to generate iPSC lines with different ApoE genotypes (isogenic, E2, E3 or E4 alleles), which have been differentiated into various cell lineages (astrocytes, neurons, macrophages, microglia). For more information, please visit:

https://doi.org/10.1016/j.scr.2018.04.011

disease-model-non-clinical-adapted-1 ADAPTED

 

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