Nature Medicine, one of the most esteemed journals in the medical field, published the research of Assoc. Prof. Dr. Selçuk Özdemir, a faculty member at the Atatürk University Faculty of Veterinary Medicine. This study will serve as a source of optimism for patients with ALS and dementia.

A spectrum of neurodegenerative diseases, including FTD, ALS, and PSP, is characterised by dementia, behavioural symptoms, paralysis and muscle loss, movement impairment, and other severe disorders. These diseases are believed to afflict as many as 60,000 people living in Germany and Turkey. These diseases result in severe health complications, despite their relative rarity.

New Diagnostic Options Are Provided by Research Based on Data from Turkey, Germany, and Spain

Assoc. Prof. Dr. Selçuk Özdemir stated in his explanation of the study, "There is currently no cure for any of these diseases." The molecular pathology of these diseases cannot be definitively diagnosed throughout the patient's life with the current methods, as brain tissue must be thoroughly examined. For the purpose of developing treatments and classifying patients according to their illnesses, it is necessary to diagnose the underlying pathology. Only this classification enables the testing of targeted and, as a result, potentially effective disease-modifying therapies.

Blood markers are capable of detecting ALS and PSP neurological diseases, as well as rare forms of dementia.

The present study has demonstrated that blood testing can identify the vast majority of ALS cases, with the exception of a specific mutation, and PSP, the behavioural variant of FTD. This also pertains to the underlying pathology. This research is the first to exhibit pathology-specific biomarkers. Most likely, the application will be in the research and therapy development phase at the outset. Nevertheless, I believe that it is feasible to employ these biomarkers for diagnostic purposes in the standard medical practice in the long term; however, additional research is required. Specifically, it will be crucial to ascertain the longitudinal development of these biomarkers, i.e., the extent to which they emerge early in the course of the disease.

Protein Detection

"This blood test is particularly necessary for the 'behavioural variant of FTD' being investigated," Özdemir stated that the new blood test, which is based on the measurement of proteins called Tau and TDP-43 proteins, offers the possibility of providing decisive evidence for diagnosis. This is because the symptoms of the most prevalent form of FTD can be attributed to two distinct pathologies (i.e., aberrant processes) in the brain, which are typically only differentiable through tissue analysis after death. DNA analysis can only guarantee certainty during the patient's lifespan in a small number of cases where the disease is genetic. The blood test that was devised in our current study now enables a definitive diagnosis to be made during the patient's lifetime, regardless of the presence of any mutations. This is a necessary condition for the evaluation of new remedies against the diverse pathologies of FTD in clinical trials.

Clusters that are abnormal

Assoc. Prof. Dr. Selçuk Özdemir stated, "It is widely recognised that Tau and TDP-43 proteins are essential in the development of FTD, ALS, and PSP, and they generate abnormal clusters in the brain." Nevertheless, the symptoms of the diseases are distinct. These disease processes are reflected in the blood levels of the proteins, as demonstrated by our investigation. We discovered that the diagnosis of behavioural FTD and its subtypes necessitates a combination of both markers. TDP-43 is enough to diagnose ALS, while tau protein is enough to diagnose PSP. Nevertheless, we are examining two distinct variants of the tau protein, known as isoforms, in relation to the tau marker.

Extracellular Vesicles

In reference to the method's uniqueness, Özdemir stated, "This is due to the fact that proteins are not directly measured in blood plasma." The results of these measurements were equivocal, particularly because tau proteins that are circulating freely in the blood are typically fragmented. The levels of two forms of tau proteins and TDP-43 proteins within vesicles, which are small lipid bubbles secreted by body cells and can eventually penetrate the bloodstream, were instead determined by our colleagues. The multi-stage preparation, which included the centrifugation of blood samples, enabled us, as researchers, to capture the proteins in the vesicles. I would like to express my gratitude to our Rector, Prof. Dr. Ömer Çomaklı, as well as my teammates, faculty members, and all those who believed in me. Specifically, I would like to thank our Rector, Prof. Dr. Ömer Çomaklı, for his support and the opportunities he provided me with, which facilitated the completion of this significant study.

Origin:

https://www.nature.com/articles/s41591-024-02937-4

CORPORATE COMMUNICATION DIRECTORATE - June 28, 2024