ADAPTED - Alzheimer’s Disease Apolipoprotein Pathology for Treatment Elucidation and Development
European Comission (H2020-JTI-IMI2-2015-05)
ADAPTED investigates the biological mechanisms through which the presence of the APOE gene increases the risk of developing Alzheimer's.
Fundació ACE-Barcelona Alzheimer Treatment & Research Center Foundation has been chosen by the European consortium Innovative Medicines Initiative (IMI) to lead the ADAPTED (Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development) research.
In view of the lack of drugs that slow down the progress of the disease, ADAPTED is opening a new line of research on the origin of Alzheimer's. The aim of the study is to systematically address APOE as a possible treatment target. The APOE gene is a known risk factor for the disease, but it has so far received less attention from researchers than other targets.
The APOE gene is a protein involved in the transport of cholesterol. Carrying the genetic variant known as APOE4 is one of the most important risk factors for developing Alzheimer's. Although this fact has been known for more than twenty years, the molecular mechanisms by which this happens are still unknown, since it has received less attention from the scientific community so far.
In particular, the behaviour of the APOE gene in the onset of Alzheimer's is unknown. This lack of understanding of how it works has meant that, until now, this gene has been largely ignored in the search for treatments.
With a budget of 7 million euros, the intention of this study, which extends the traditional lines of research on Alzheimer's and which is coordinated by Fundació ACE, is to identify how APOE increases the risk of suffering from Alzheimer's and, in this way, to enable the development of new drugs.
With ADAPTED, Fundación ACE becomes the first Spanish entity to be chosen to coordinate, at the same time, two European researches on the origin of Alzheimer. It should be remembered that the IMI has also chosen the entity to coordinate another European study whose purpose is to identify effective mechanisms for the early detection of Alzheimer's (MOPEAD).
Gene present in 45% of cases
The APOE gene is present in more than 45% of Alzheimer's cases and, for this reason, according to Dr. Agustín Ruiz, Research Director at Fundació ACE, "understanding the function of APOE is a major scientific challenge". Ruiz points out that "if the project is successful, the treatment and prevention of Alzheimer's disease will enter a completely new era of drug and therapy identification".
Currently, through a DNA analysis, it is possible to observe the behavior of this gene and identify the percentage of risk a person has of suffering from Alzheimer's. For example, an individual with two copies of the gene's epsilon 2 allele would have a 6% chance of developing the disease. However, someone with two copies of another variant of the gene (the epsilon 4 allele) would have more than 50%.
Since its inception, the accumulation of beta-amyloid protein in the brain has been considered one of the causes of the appearance of the disease. Work on this thesis will continue in the exploration of the protein, in parallel with the genetic research that opens with the new study.
Sponsors / Funders
IMI (Innovative Medicines Initiative) - public-private partnership between the EU and the European Federation of Pharmaceutical Industries and Associations (EFPIA)
Project leader at Fundació ACE
Doctor Agustín Ruiz, Research Director
- Fundació ACE
- Agencia Estatal Consejo Superior Deinvestigaciones Cientificas (Instituto Cajal y Centro Nacional de Biotecnología)
- DC Biosciences (DCP)
- Erasmus Medical Centre (EMC)
- Modus Research and Innovation (MOD)
- Leiden University (UL)
- Unviversitaetsklinikum Bonn (UKB)
- Klinikum Der Universitaet Zu Koeln, Cologne (UKK)
- Centro Andaluz de Estudios Bioinformáticos (CAEBi)
- MIM (Mimetas B. V.)
- Janssen Pharmaceutica
Links of interest
- Project website.
- Project information.
- IMI consortium website.
IMI (Innovative Medicines Initiative)
- Meet the ADAPTED Researchers
Dr. Agustín Ruiz, Fundació ACE
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease.
Nat Genet 49, 1373–1384 (2017). https://doi.org/10.1038/ng.3916.
Sven J van der Lee, Gerard D Schellenberg, Agustín Ruiz et al.
Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer’s disease.
Sci Rep 9, 16665 (2019). doi: https://doi.org/10.1038/s41598-019-52724-2.
Agustín Ruiz, Sonia Moreno-Grau, Itziar de Rojas, G. Monté- Rubio, Adela Orellana, Sergi Valero et al.
PLCG2 protective variant p.P522R modulates tau pathology and disease progression in patients with mild cognitive impairment.
Acta Neuropathol 139, 1025–1044 (2020). doi: https://doi.org/10.1007/s00401-020-02138-6.
Agustín Ruiz, Ana Espinosa, Isabel Hernández, Itziar de Rojas, Adelina Orellana, Sergi Valero, Mercè Boada et al.
CDH6 and HAGH protein levels in plasma associate with Alzheimer’s disease in APOE ε4 carriers.
Sci Rep 10, 8233 (2020). doi: https://doi.org/10.1038/s41598-020-65038-5.
Cornelia M. van Duijn, Agustín Ruiz et al.