A study published in the prestigious scientific journal Nature Medicine has identified the first biomarker that allows the detection of the underlying neuropathology in frontotemporal dementia (FTD) and differentiates the two proteins that accumulate in the brain in this neurodegenerative disease. Researchers from the Neurobiology of Dementias group and the Memory Unit at the Sant Pau Research Institute (IR Sant Pau), led by Dr. Juan Fortea, have played a key role in this research, which opens new avenues for differential diagnosis compared to other neurodegenerative pathologies, such as amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP), representing a step forward in patient classification, in the design of more specific clinical trials, and, therefore, in the development of future therapies.
“Frontotemporal dementia is a very complex and very heterogeneous disease from the clinical, genetic, and neuropathological point of view, that is, in terms of the alterations that occur in the brain,” explains Dr. Oriol Dols-Icardo, a researcher in the Neurobiology of Dementias group and the Memory Unit at IR Sant Pau. “In frontotemporal dementia, these alterations are caused by the accumulation of two types of proteins: tau and TDP-43. There was an urgent need for non-invasive biomarkers because, until now, we could only know which of the two proteins was accumulating in the brain post-mortem. Now, with this first biomarker, we can differentiate them in the patient’s life with a blood test and a diagnostic accuracy of over 90%.”
The study has demonstrated that extracellular vesicles (EV) present in blood plasma contain quantifiable amounts of tau and TDP-43 proteins, which are key in differentiating the type of neurodegenerative pathology, for example, in the case of frontotemporal dementia and ALS. In this regard, according to Dr. Dols-Icardo, “in ALS, 97% of patients accumulate TDP-43 in the brain, while in the case of frontotemporal dementia, this percentage is around 50%, and another 45% corresponds to the tau protein.” Furthermore, “the research has also shown that there is a very clear correlation between the amount of tau or TDP-43 protein accumulated in the brain and neuronal damage and severity.”
In the field of research, the identification of this first biomarker represents a very significant step forward because it will allow for a more precise classification of patients and the specific study of each protein’s accumulation in the brain, meaning that “we will be able to design and conduct more specific clinical trials -genomic, proteomic…- depending on the pathology and the characteristics of each of these patients. And this is crucial because there are treatments directed at one protein or the other, and we will be able to offer both more personalized research and medicine.”
The research published in Nature Medicine analyzes data from 991 adults. Specifically, 704 patients participated, including 68 cases confirmed genetically or neuropathologically. The study’s results have been replicated and validated in an independent cohort from the Memory Unit of Sant Pau Hospital, with 287 participants, which reinforces the robustness of the findings.
The study has been led by the Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), a research institute for neurodegenerative diseases, and also involved the University Hospital of Bonn (UKB) and other research institutions in Germany.
