Tauopathies, a group of neurodegenerative diseases that includes progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), remain one of the major diagnostic challenges in neurology today. In their early stages, they can present with highly diverse symptoms and overlap with other neurodegenerative disorders, making it difficult to accurately identify the underlying disease and delaying the development of treatments aimed at modifying its course.
A project led by Dr. Jesús García-Castro, a researcher at the Institut de Recerca Sant Pau (IR Sant Pau) and a neurologist at the Sant Pau Memory Unit, has received a Next-Generation Research Grant in Frontotemporal Dementia. This is an international grant promoted by the American Academy of Neurology Institute, the American Brain Foundation, and The Association for Frontotemporal Degeneration. The award will fund a two-year study focused on the development and validation of new biomarkers to improve the diagnosis and monitoring of these diseases.
“One of the major challenges in these disorders is that the definitive diagnosis still depends, in numerous instances, on neuropathological examination,” explains Dr. Jesús García-Castro. “Having reliable biomarkers that allow the disease to be identified during a patient’s lifetime is an essential step toward improving clinical management and advancing the development of new treatments.”
The project proposes an innovative strategy based on the combination of blood biomarkers and advanced magnetic resonance neuroimaging analysis, with the aim of improving the identification of tauopathies in the early stages of the disease. Specifically, the study will analyze the presence of different isoforms of the tau protein in extracellular vesicles present in plasma, small particles released by cells that transport proteins and other molecules. This can reflect pathological processes occurring in the brain. The proportion of tau isoforms associated with these vesicles could provide relevant information about the type of neurodegenerative pathology present in each patient.
These data will later be integrated with structural magnetic resonance imaging analysis models capable of identifying specific patterns of brain atrophy in cortical and subcortical regions involved in tauopathies. The combination of both approaches will allow the development of a two-stage diagnostic algorithm to facilitate a more precise identification of these diseases.
“Each of these tools provides different information about the disease. Integrating blood biomarkers and neuroimaging data can help us better understand the biological mechanisms of tauopathies and improve their identification in clinical practice,” explains García-Castro.
The study will rely on the analysis of data from large international research cohorts in neurodegenerative diseases, including participants from initiatives such as 4RTNI, UCSF, and the SPIN (Sant Pau Initiative on Neurodegeneration) cohort. Longitudinal analysis of these patients will allow researchers to evaluate not only the diagnostic performance of the biomarkers but also their usefulness in predicting the clinical progression of the disease and better understanding the factors that influence its progression.
“These types of tools can also be key for clinical research, because they will allow us to identify patients more precisely and better track disease progression,” says García-Castro. “This is especially relevant for the development of future clinical trials aimed at modifying the course of these disorders.”
The Next-Generation Research Grant in Frontotemporal Dementia is an international initiative aimed at supporting investigators in the early stages of their scientific careers and promoting advances in the understanding of frontotemporal dementias.
The project will be carried out within the multidisciplinary environment of IR Sant Pau, under the mentorship of Dr. Ignacio Illán-Gala, an expert in neuroimaging biomarkers and neurodegenerative diseases, and with the participation of researchers from the Sant Pau Memory Unit. This is within the framework of research lines dedicated to the study of frontotemporal dementias and other neurodegenerative diseases.
