Blood Markers Detect Rare Forms of Dementia, Other Neurodegenerative Diseases

Frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and progressive supranuclear palsy (PSP) are neurodegenerative diseases that present severe health consequences, including dementia, behavioral symptoms, paralysis, muscle wasting, and movement impairments. A recent study by scientists at the German Center for Neurodegenerative Diseases (DZNE), demonstrates that these conditions can be identified through blood tests, potentially revolutionizing diagnosis and therapy development.

The study, published in Nature Medicine, showcases that specific proteins in the blood can serve as biomarkers for these diseases. Although the procedure is not yet ready for routine medical use, it holds promise for facilitating diagnosis and advancing new therapies. The research involved collaboration with the University Hospital Bonn (UKB) and other institutions in Germany and Spain.

According to researchers, FTD, ALS, and PSP form a spectrum of diseases with overlapping symptoms. In Germany, approximately 60,000 people are affected by one of these conditions. Despite their rarity, the impact on health is significant, and no cure currently exists.

“As yet, there is no cure for any of these diseases. And, with current methods, it is not possible to reach a conclusive diagnosis of the molecular pathology of these diseases during a patient’s lifetime, since brain tissue must be examined,” explained Anja Schneider, MD, a research group leader at DZNE and Director of the Department of Old Age Psychiatry and Cognitive Disorders at UKB.

The research focused on measuring tau and TDP-43 proteins in the blood. According to the study, these proteins, known to form abnormal aggregates in FTD, ALS, and PSP, are crucial for diagnosing and understanding these diseases. The study found that a combination of both markers is required to diagnose behavioral FTD and its subtypes, while TDP-43 alone is sufficient for ALS, and tau proteins for PSP.

“It is well known that tau and TDP-43 proteins play key roles in FTD, ALS and PSP, as they form abnormal aggregates in the brain in these diseases. The events differ between the diseases, however,” said Dr. Schneider. “Our investigations suggest that blood levels of the proteins reflect these disease processes.”

The innovative approach involves measuring these proteins within vesicles—tiny lipid bubbles secreted by cells that enter the bloodstream. This method overcomes the limitations of direct blood plasma measurements, which can be inconclusive due to protein fragmentation. The findings are based on data and blood samples from study collectives in Germany and Spain, including over 700 patients from the DESCRIBE cohorts and over 200 participants from the Sant Pau cohort in Barcelona.

“We have found that the combination of both markers is required for the diagnosis of behavioral FTD, respectively its subtypes, whereas TDP-43 is sufficient for ALS and the tau protein for PSP,” said Dr. Schneider. “However, for the tau marker, we are actually looking at two specific variants, so called isoforms, of the tau protein.”

Though further studies are needed to determine how these biomarkers develop over time and their early presence in the disease course, researchers say the potential for these biomarkers to be used in routine diagnosis is promising. This advancement could pave the way for more effective, targeted treatments and significantly improve patient outcomes.