In the present project, we have isolated and characterized morphologically and content-wise EVs from post-mortem brain tissue of sporadic AD and healthy controls. To do so, we had to improve and validate a new method to isolate them from the tissue since the available approaches were damaging certain protein content of the sample, which is crucial for understanding their role in AD. The development of this improved approach will be helpful in studying the role of EVs in the brain in a closer-to-reality way. The EVs isolated from AD tissues with this new methodology displayed AD-related protein hallmarks, demonstrating their potential role in the pathophysiology of the disease.
Moreover, to validate the role of these EVs in the brain cells, we established an in vitro model of neurons derived from human-induced stem cells (iPSC). These iPSCs come from healthy and AD patient donors and allow us to have a reliable human brain model in a dish. With that, we have studied how the EVs can regulate the Aβ-derived pathology and protect the neurons from it. Finally, we have validated the role of a particular protein present in the EVs, the Prion protein (PrP), in the Aβ aggregation, pointing to its role in forming the amyloid plaques, a potential natural neuroprotective mechanism.
To sum up, the results derived from this project brought valuable knowledge about EVs in the brain, especially in the context of AD progression. Our new methodology and EV characterization have defined their interesting role in the Aβ modulation and its derived toxicity, making them putative candidates for natural neuroprotective mechanisms. All this data could also be used to study potential biomarkers of the pathology in EVs from accessible biofluids (such as the blood or urine), which could improve the AD prognosis and diagnosis.
Regarding my career, the project has allowed me to integrate into the National and International scientific community, especially in the EV field. I have become an active member of the Spanish, German, and International Societies of Extracellular Vesicles. For instance, I co-organized the first EV Meeting for EV researchers in the Hamburg region. And now, I am co-organizing the annual meeting of the German Society of Extracellular Vesicles in my city, Hamburg. In this regard, I attended five conferences related to Alzheimer`s disease and EVs, to which I have been invited twice to make an oral communication. The project has also been distributed to the general public, especially kids and teenagers, with seven seminars in different schools and high schools in Spain, where more than 250 students attended. Furthermore, the project has also produced, so far, two peer-reviewed publications and two more will be released soon. One is already being reviewed in a high-impact factor journal.
