In a recent study involving 991 adults, researchers at DZNE have demonstrated the potential of blood testing to identify common forms of frontotemporal dementia (FTD), as well as the neurological disorders amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP). Published in “Nature Medicine,” the findings highlight the use of specific blood proteins as biomarkers for these conditions, although the method is not yet ready for routine clinical use. Nevertheless, it holds promise for enhancing disease diagnosis and accelerating the development of new therapeutic strategies.
FTD, ALS, and PSP collectively represent a spectrum of debilitating neurodegenerative diseases characterised by symptoms such as dementia, behavioural changes, paralysis, muscle deterioration, and impaired movement. In Germany alone, an estimated 60,000 individuals are affected by these diseases, which, despite their rarity, impose severe health burdens. Definitive diagnosis of the molecular pathology underlying these conditions typically requires post-mortem brain tissue analysis, presenting a significant clinical challenge.
Professor Anja Schneider, a research group leader at DZNE and Director of the Department of Old Age Psychiatry and Cognitive Disorders at UKB, underscores the critical need for diagnostic markers to elucidate disease pathology. She explains that stratifying patients based on disease pathology is essential for developing targeted therapies, which currently need improvement due to existing methods’ diagnostic limitations.
The study reveals that blood tests measuring tau and TDP-43 proteins can effectively identify PSP, the behavioural variant of FTD, and most ALS cases, except for those involving specific mutations. These biomarkers offer a novel approach to diagnosing the underlying pathology of these diseases during a patient’s lifetime, potentially transforming clinical management and therapeutic research.
Schneider emphasises the importance of longitudinal studies to track the development of these biomarkers throughout disease progression. Understanding how these markers evolve could provide crucial insights into early disease detection and intervention strategies, improving patient outcomes.
The innovative blood test technique measures tau and TDP-43 proteins encapsulated within lipid vesicles secreted by cells. Different from direct measurement of free-floating tau proteins in blood plasma, which proved inconclusive, this method involves isolating these proteins via multi-stage preparation, including centrifugation of blood samples. This approach enhances the accuracy and reliability of biomarker detection, facilitating robust validation across diverse study cohorts in Germany and Spain.
Collaborative efforts involving multiple research institutions and patient cohorts were instrumental in validating these findings. The study drew upon data and blood samples from over 700 patients in Germany and more than 200 participants in Spain, reflecting a concerted international effort to overcome the challenges posed by the rarity of these diseases and ensure statistically robust conclusions.
The results underscore the significance of collaborative medical research in advancing diagnostic capabilities and therapeutic avenues for complex neurodegenerative diseases. By elucidating the role of tau and TDP-43 proteins in FTD, ALS, and PSP, the study paves the way for future clinical applications of blood-based biomarkers in disease diagnosis and treatment evaluation. While further research is necessary to refine and validate these findings, the potential impact on improving patient care and accelerating therapeutic development is profound.
More information: Madhurima Chatterjee et al, Plasma extracellular vesicle tau and TDP-43 as diagnostic biomarkers in FTD and ALS, Nature Medicine. DOI: 10.1038/s41591-024-02937-4
Journal information: Nature Medicine Provided by DZNE – German Center for Neurodegenerative Diseases
