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Meet the ADAPTED Researchers - Dr. Santos Mañes, CNB-CSIC

What is your role within the ADAPTED Project?

As part of the ADAPTED cell research group, we are aiming to characterise how the different APOE isoforms affect several functional parameters in monocytes and macrophages, including their polarization, cholesterol influx/efflux capacity and their crosstalk with the endothelium.

Tell us a bit more about the CNB CSIC.

The Spanish Research Council (CSIC) is the largest public research institution in Spain and the third largest in Europe. The National Center for Biotechnology (CNB) is a strategic institute of CSIC devoted to multidisciplinary research for the generation of scientific knowledge and its application to human and animal health issues, as well as environmental and agricultural challenges. The CNB is one of the eight Research Excellence Institutes “Severo Ochoa” in Life Sciences and Medicine in Spain.

What have been some of the biggest achievements/breakthroughs so far in the project?

We have found an unexpected link between the expression of the chemokine receptor CX3CR1 in monocytes and the APOE status, specifically in Alzheimer’s disease patients. This may indicate a particular and specific APOE-induced inflammatory milieu in these patients, which may also affect the functionality of these cells before and after differentiation to macrophages.

We have also found that APOE status affects the lipidic profile of plasma, which may have repercussions in Alzheimer’s disease-associated comorbidities. Preliminary results suggest that APOE function in macrophages contributes to these lipidome alterations.

What excites you most about the project?

The multidisciplinary scientific team, which includes geneticists, molecular and cellular biologists, immunologists, and bioinformatics. The extensive use of ‘Omics, which includes metabolomics, proteomics, transcriptomics and epigenomics, and the possibility to integrate all this information to clarify what is the role of APOE in Alzheimer’s Disease (AD).

What are your expectations for ADAPTED?

To identify new molecular pathways induced deferentially by APOE isotypes in macrophages, and to clarify whether or not cholesterol efflux can be associated to an specific APOE genotype and its influence in the diagnosis and progression of Alzheimer’s Disease.

What are your hopes for the future treatment of Alzheimer’s disease?

Evidence suggests that metabolic alterations and cardiovascular diseases are strongly associated with Alzheimer’s disease onset and evolution. My hope is that the new knowledge generated around the inflammatory status associated with specific APOE genotypes will help in the design of new therapeutic strategies to decrease the incidence of AD and/or attenuate its progression.

What do you think EU collaborative research projects have to offer?

This type of project is a great opportunity to collaborate with researchers that have a similar mindset but different skills, which thus accelerates the success of a multidisciplinary research project. The inclusion of the Pharmaceutical Industry in these collaborative projects opens a window to do a transnational research and accelerates the transfer of technology.

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