Scientists have identified signs of Huntington's disease before symptoms appear

Huntington's disease can develop unnoticed for years: a person is already a carrier of a genetic mutation, but has not yet experienced motor or cognitive impairments. In this case, changes in the nervous system may begin earlier than they can be detected using standard examinations. The researchers found signs of neuron damage in some of the mutation carriers at the earliest stage of the disease. The information about which protein helped to identify these changes and what they can tell about the development of the disease can be found in the Izvestia article.

Damage to neurons before the first symptoms

A study by specialists from the Sant Pau Hospital Research Institute in Barcelona has been published in the journal Movement Disorders. The researchers analyzed data from 296 people from two groups. The researchers compared biomarker values in blood and cerebrospinal fluid with the results of clinical examinations and neuroimaging.

The team paid special attention to the light chain of neurofilaments, the NfL protein, which enters biological fluids when nerve cells are damaged. Its concentration can serve as an indicator of damage to neurons, although in itself it does not indicate a specific cause of such a process.

The scientists used the HD-ISS Huntington's disease staging system. It includes four stages of the disease development. At stage zero, a person already has a disease-causing mutation, but there are no clinical symptoms or detectable structural changes in the brain yet. It was at this stage that the researchers found signs of nerve cell damage in some of the participants.

The NfL protein indicated early changes

In the first group, increased levels of NfL in the cerebrospinal fluid were found in 78% of participants with stage zero disease. In blood plasma, the indicator was higher than the reference threshold in 59% of people. In the second group, an increased protein concentration in the cerebrospinal fluid was detected in 53% of participants at the same stage.

Thus, in some carriers of the mutation, signs of neuron damage were already present, although there was no visible brain atrophy and clinical disorders yet. This indicates that people who are formally at the same early stage of the disease may differ in the biological state of the nervous system.

What can the NfL tell us about the development of the disease?

Participants with elevated levels of NfL were, on average, closer to the expected onset of clinical manifestations of the disease. According to prognostic models, the estimated time to onset of symptoms in different groups and depending on the type of biological sample was about 10-13 years. In people with protein levels below the reference threshold, the score reached about 23-24 years of age.

The authors emphasize that these values are obtained using mathematical models. They do not mean that the researchers observed each participant before the onset of symptoms and established the exact date of their occurrence. This is a statistical estimate that shows the relationship between protein concentration and the estimated proximity of the clinical onset of the disease.

Scientists have linked sleep quality and brain health in chronic diseases

Why is the blood test still not giving a complete picture?

The researchers found a close relationship between the concentration of NfL in blood plasma and cerebrospinal fluid. This opens up the possibility of using a routine blood test to study early changes in more people. However, within the framework of this work, the indicators of cerebrospinal fluid better distinguished the earliest stages of the disease.

In addition to NfL, the scientists evaluated mutant huntingtin, a protein directly linked to the genetic cause of the disease, and a common tau protein. Mutant huntingtin could be detected already at the zero stage, but its concentration was too low for accurate measurement. The total tau protein increased more noticeably at a later stage associated with functional disorders.

The authors believe that biomarkers can complement the existing HD-ISS staging system and help more accurately describe the biological state of people with the mutation. However, before using such indicators more widely, it is necessary to confirm the reference values and check how reliably they allow predicting real clinical changes.

Thus, the work shows that neuron damage in some carriers of the mutation can begin earlier than symptoms or noticeable brain atrophy appear. At the same time, elevated NfL cannot yet be considered an independent diagnostic method or an accurate prognosis of the disease: the results require further verification.