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New Blood Test Enables Accurate Diagnosis of Dementia and Neurological Diseases

By LabMedica International staff writers
Posted on 24 Jun 2024
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Image: Scientists have identified blood biomarkers for FTD, ALS and PSP (Photo courtesy of DZNE/Frommann)
Image: Scientists have identified blood biomarkers for FTD, ALS and PSP (Photo courtesy of DZNE/Frommann)

Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy (PSP) represent a group of neurodegenerative diseases with symptoms that include dementia, behavioral changes, paralysis, muscle wasting, and movement impairments. These diseases are rare but have severe health impacts, and currently, there are no cures. Presently, conclusive diagnosis of the molecular pathology of these diseases during a patient's lifetime is challenging because it typically requires examination of brain tissue. However, accurate diagnosis is essential for developing therapies and for patient stratification, which is necessary for testing targeted disease-modifying treatments. Now, researchers have demonstrated that the most common forms of FTD, as well as ALS and PSP, can be detected through blood tests, though these tests are not yet ready for routine clinical use. In the long term, they could significantly improve disease diagnosis and accelerate the development of new treatments.

This research, led by the German Center for Neurodegenerative Diseases (DZNE, Bonn, Germany), involved measuring specific proteins in the blood that act as biomarkers. The innovative blood test focuses on tau and TDP-43 proteins, providing crucial diagnostic information. The study analyzed data and blood samples from 991 adults in Germany and Spain, including individuals affected by FTD, ALS, PSP, and a control group of healthy individuals. This setup allowed for extensive validation of the findings across independent volunteer groups. The approach involves a novel method where these proteins are not directly measured in the blood plasma, as previous attempts to do so were inconclusive; the tau proteins found in blood are often fragmented. Instead, the levels of two forms of tau proteins and TDP-43 proteins are measured inside vesicles—tiny lipid bubbles secreted by body cells that enter the bloodstream. By using a multi-stage preparation process, including the centrifugation of blood samples, the researchers could isolate the proteins contained in these vesicles.

This study primarily addressed the "behavioral variant of FTD," the most common type of FTD, which can arise from two different brain pathologies only distinguishable after death through tissue analysis. Typically, only genetic cases of the disease can be definitively diagnosed during a patient's lifetime through DNA analysis. The new blood test, however, allows for precise lifetime diagnoses even in non-genetic cases. This advancement is crucial for the clinical trials testing new therapies against different FTD pathologies.

“We now show that PSP, behavioral variant of FTD and the vast majority of ALS cases with the exception of a particular mutation can be recognized by blood testing and this also applies to their underlying pathology,” said Prof. Anja Schneider, a research group leader at DZNE. “Our study is the first to find pathology specific biomarkers. Initially, application is likely to be in research and therapy development. But in the long term, I consider it realistic that these biomarkers will also be used for diagnosis in medical routine. However, further studies are required for this. In fact, it would be particularly important to determine how these biomarkers develop longitudinally, that is, over the course of a disease, and how early they rise in the disease course.” The findings of the study were published in Nature Medicine on June 18, 2024.

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