On April 29, the Barcelonaβeta Brain Research Center (BBRC) researcher Marta Milà defended her doctoral thesis on profiles of fluid biomarkers in the preclinical stage of Alzheimer's.
The thesis, entitled 'Characterization of fluid biomarker profiles in the preclinical stage of the Alzheimer's continuum', is the third to be carried out within the framework of the BBRC's Alzheimer's research program, and delves into current knowledge of the disease during its preclinical stage. To carry out the research, Milà used data from 2,743 participants from the ALFA and 450 from the ALFA+ study, in addition to other cohorts.
The objectives of the thesis have been, on the one hand, to study the impact of different definitions of amyloid beta positivity based on biomarkers and, on the other, to elucidate the pathophysiological phenomena that occur in preclinical Alzheimer's and how they are affected by factors. non-modifiable risk factors, such as age and sex. In addition, the researcher has studied the performance of new biomarkers in blood to detect preclinical Alzheimer's. Its directors have been the BBRC researcher Dr. Marc Suárez and Dr. José Luis Molinuevo, honorary member and scientific consultant of the center.
We spoke with her to learn more about her thesis and her future projects.
What are the main conclusions of your thesis?
In relation to the pathophysiological pathways that characterize the preclinical phase of Alzheimer's, the results have shown that once alterations in beta-amyloid protein levels occur, the levels of other multiple biomarkers that reflect the activation of different pathophysiological processes in brain. In addition, we have seen that the most important risk factors for Alzheimer's, such as age, female sex or being a carrier of APOE-ε4, have a modifying role in these pathophysiological mechanisms.
Regarding the study of new biomarkers in blood and their accuracy to detect the preclinical phase of Alzheimer's, we have concluded that various biomarkers of amyloid protein, tau, inflammation and axonal damage are increased in blood in preclinical Alzheimer's. Specifically, new isoforms of the tau protein in blood show the greatest precision for the early detection of the disease.
In summary, the results of the thesis provide new evidence for the early detection of Alzheimer's, with very relevant implications for improving the design of clinical studies aimed at preventing the onset of symptoms and also for clinical practice.
How do you face your new stage as a postdoctoral researcher? What lines of research would you like to delve into from now on?
I am starting my stage as a postdoctoral researcher in the Fluid Biomarkers and Translational Neurology group at the BBRC, where we have various projects related to the study of fluid biomarkers and their usefulness in predicting changes at the cognitive level, as well as their association with biomarkers of neurodegeneration in neuroimaging. Later, I would like to dedicate some time of my research career to work in a foreign research center, to gain new knowledge and international experience within the same field of research.
The lines of research that I would like to delve into are, on the one hand, working towards the implementation of blood biomarkers for Alzheimer's disease, which offer a less invasive and more accessible option for participants in clinical studies and for patients. On the other hand, I would also like to further study the effect of risk factors on the development of Alzheimer's disease. One of these factors, which has not been extensively studied, is sex. In this sense, I am very interested in analyzing and better understanding the differences between men and women in the risk of developing Alzheimer's, as well as in its pathophysiological pathways and clinical manifestations.