Early detection of ALS and frontotemporal dementia

Genetic alterations to the C9orf72 gene are associated with frontotemporal dementia (FTD) and ALS. Researchers of VIB, KU Leuven and UZ Leuven have discovered that a specific type of PET scan can detect brain changes in people with an altered C9orf72 gene even before they become ill. According to Prof. Dr. Philip Van Damme, head of the research team, the results suggest that the imaging technique can detect early changes years before the disease starts.

The study investigated patients in an early, presymptomatic disease phase. Joke De Vocht, PhD student in the research group of Prof. Dr. Philip Van Damme (UZ Leuven and VIB-KU Leuven): "Using advanced FDG-PET-MR brain scans, we can identify changes at the individual level even before the first signs of the disease appear".

C9orf72 mutations cause frontal lobe dementia and ALS

The researchers discovered that genetic changes at the level of the so-called C9orf72 gene are the main cause of both ALS and FTD. This shows that both disorders form two extremes of the same continuum.

Prof. Dr. Philip Van Damme, neurologist at UZ Leuven: "A C9orf72 gene mutation is the most common cause of both hereditary ALS and FTD, but the mutation is accompanied by an extremely variable clinical phenotype, and does not always seem to cause the disease. This suggests that there are several factors that can positively or negatively influence the disease process. These factors are of course interesting therapeutic targets.”

The study of presymptomatic individuals offers enormous opportunities to better understand the disease process of age-related neurodegenerative diseases.

Prof. Dr. Philip Van Damme - neurologist in UZ Leuven

People who are carriers of the specific genetic modification in the C9orf72 gene represent an interesting study population for research, because many of them are future patients. Prof. Dr. Van Damme: "The study of presymptomatic individuals offers enormous opportunities to better understand the disease process of age-related neurodegenerative diseases".

FDG-PET as an early biomarker for changes in the brain

The findings are very important for the development of new treatment strategies that could slow down or even prevent the disease. "As an early and sensitive biomarker, the FDG-PET scan can help determine the best time to start preventive treatments".

More information about ALS and FTD

Gene alterations or mutations in C9orf72 are the most common cause of hereditary amyotrophic lateral sclerosis (ALS) and frontotemporal or frontal lobe dementia (FTD).

In ALS, also known as motor neurone disease (MND) or Lou Gehrig's disease, so-called motor neurons (nerve cells that control muscles) are increasingly dying off, resulting in a gradual weakening of the muscles themselves. The majority of ALS patients die within two to five years of the first appearance of symptoms. Approximately half of all patients also show non-motor symptoms.

FTD is, after Alzheimer's disease, the most common form of dementia at a young age. It is accompanied by changes in cognition (e.g. language) and behaviour (e.g. apathy) due to the loss of nerve cells in the frontal and temporal lobes of the brain.

(Based on a press release by VIB)

Read the original publication in JAMA Neurology (De Vocht et al. 2020)