A study published in Nature Aging looked at a large number of proteins in cerebrospinal fluid (CSF) to see if combinations of changes in these proteins could be used for indicating severity or presence of frontotemporal dementia (FTD) in the future. The research was led by Dr. Rowan Saloner, a current AFTD grant recipient, and included several other scientists supported by or involved with AFTD’s Medical Advisory Council. 

Looking for Better Tools to Understand FTD Severity

It is difficult for healthcare professionals to detect FTD due to its varied symptomology and a lack of biomarkers. It can also be difficult for doctors to track the severity of FTD, which could help them assemble a more fitting treatment plan. The study aimed to identify protein changes which might be useful as biomarkers that can help diagnose and track the severity of FTD more precisely. 

To do this, researchers analyzed CSF samples from people enrolled in the long-term ALLFTD study. The research team studied a group of participants who carry a genetic increased risk of FTD and compared them to people without a risk gene (but who had a family history of genetic FTD) as a control group. The team also looked at two additional groups—one with a non-genetic case of an FTD disorder called PSP-Richardson syndrome (PSP-RS), and another from the Swedish BioFINDER 2 study, which included people with FTD, Alzheimer’s, and healthy controls. 

What the Researchers Found 

In total, researchers studied over 4,000 proteins in participants’ CSF samples. Using computer analysis, they found 31 groups of proteins that tend to increase or decrease together. Of these, seven groups were found to correspond with FTD severity. These proteins were related to important brain functions like how neurons communicate and how genetic material is processed. 

Some of these protein changes were found even in people who hadn’t yet developed symptoms, suggesting that the disease may start causing changes in the brain before it becomes noticeable. 

When the team looked at people with PSP-RS and Alzheimer’s, they saw similar patterns, although the changes were more specific and stronger in people with FTD. 

Why This Matters 

This study points to the potential for using specific proteins (and protein groups) as markers for how FTD develops and progresses—something that could improve diagnosis and treatment long-term. While more research is needed to validate the authors’ findings and develop specialized tools, a process that may take some time, these findings could pave the way for earlier and more personalized care for people living with FTD. 

Dr. Saloner, the study’s lead author, said, “I became interested in FTD after seeing how hard it can be for patients to get an accurate diagnosis, especially at such a young age. My goal is to find biological clues in the body that can help guide more effective care.” 

Dr. Saloner’s work was supported by the Clinical Research Training Scholarship in FTD, funded by the Holloway Family Fund and the American Brain Foundation, in collaboration with the American Academy of Neurology.  

AFTD is committed to biomarker development to help make diagnosis more accurate and timely. Many scientists are working on advancing different types of biomarkers, and AFTD is working to close the gap in support for this vital area of research. 

Proteomics is helping scientists better understand the biological mechanisms driving FTD; a recent example is a British study that evaluates the ability of a novel protein assay to detect and analyze blood-based biomarkers for FTD and other dementias. Another example is a study that identified a profile of inflammation-related proteins that could potentially serve as a biomarker of FTD severity.