IT HAS BEEN found that serum TDP-43 levels can help with identifying common neuropathological changes associated with frontotemporal dementia (FTD). Diagnosing FTD, which is one of the most common causes of progressive dementia in working-age people, remains challenging due to the fact that the FTD spectrum includes several subtypes that have different symptoms, neuropathology, and genetics. This new research would allow a better understanding of the neuropathological changes in patients at the diagnostic stage, which would aid the assessment of prognosis and future treatments.
Research lead Annakaisa Haapasalo, A.I. Virtanen Institute for Molecular Sciences, Kuopio, Finland, and colleagues, aimed to identify patients with FTD with TDP-43 accumulation. The researchers measured TDP-43 levels through a sensitive single-molecule array technology using patients’ blood samples. The results showed that patients with motor neurone disease, or carrying the C9orf72 repeat expansion had significantly lower serum TDP-43 levels, even though previous studies suggested that these patients typically accumulate TDP-43. Carriers of MAPT mutations, who can have tau accumulation in their brains, did not have lower levels of TDP-43.
The current diagnostic methods do not allow the differentiation of patients with TDP-43 neuropathology from patients with other frontotemporal dementia, as they are not sensitive or accurate enough. TDP-43 could therefore be a useful biomarker if researchers can develop a more specific and sensitive analysis method. Future research could also allow for a blood test to differentiate between neuropathological subtypes of FTD and other forms of dementia, allowing for a more rapid and accurate differential diagnosis, and more specific interventions that affect disease progression.