Serum TDP-43 levels can help to identify common neuropathological changes associated with frontotemporal dementia

Serum TDP-43 levels can help to identify common neuropathological changes associated with frontotemporal dementia

Frontotemporal dementia (FTD) is one of the most common causes of progressive dementia in working-age people. However, making a diagnosis and a prognosis is often challenging because the frontotemporal dementia spectrum includes several subtypes that differ in terms of symptoms, genetics and neuropathology, i.e., changes in the brain associated with the disease. Typically, proteins accumulating in the brain of patients with FTD and harming their neurons are either TDP-43 or tau proteins. Understanding the neuropathological changes in patients already at the diagnostic stage would be particularly helpful in terms of assessing their prognosis and possible future treatments.

A recent study from the University of Eastern Finland, the University of Oulu and the University of Brescia in Italy sought to identify FTD patients with TDP-43 accumulation from a large patient cohort, which included all of the most common subtypes of the disease. TDP-43 levels were measured from patients’ blood samples using a sensitive single-molecule array (Simoa) technology.

The researchers found that serum TDP-43 levels were considerably lower in patients carrying the C9orf72 repeat expansion or with motoneuron disease. Previous studies have shown that these patients typically accumulate the TDP-43 protein in their brain. Lower levels of TDP-43 were not observed in carriers of MAPT mutations, who typically have tau accumulation in their brain.

“Our current diagnostic methods are not sensitive or accurate enough to differentiate patients with TDP-43 neuropathology from other frontotemporal dementia patients. However, this study shows that TDP-43 is a potentially useful biomarker for this purpose, if more specific and sensitive analysis methods can be developed,” says Postdoctoral Researcher and Co-lead Author Kasper Katisko, MD, PhD, of the University of Eastern Finland.

In the future, it is likely that a simple blood sample can be used to differentiate between the actual neuropathological subtypes of frontotemporal dementia and other forms of dementia, too. This will make differential diagnostics increasingly rapid and accurate, enabling the development of patient-specific interventions affecting disease progression.

The findings were published in Alzheimer's Research & Therapy. The project was led by Research Director Annakaisa Haapasalo at A.I. Virtanen Institute for Molecular Sciences and by Research Director Eino Solje at the Institute of Clinical Medicine at the University of Eastern Finland.

The project was funded by the Finnish Medical Foundation, the Finnish-Norwegian Medical Foundation, the Olvi Foundation, the Maire Taponen Foundation, the Päivikki and Sakari Sohlberg Foundation, the Yrjö Jahnsson Foundation, the Finnish Cultural Foundation, the Maud Kuistila Memorial Foundation, the Finnish Brain Foundation, the Orion Research Foundation, the Instrumentarium Science Foundation, the Sigrid Jusélius Foundation, the Academy of Finland, and the Finnish Association for Supporting ALS Research. The project is part of the FinFTD consortium’s research on frontotemporal dementia.

For further information, please contact:

Postdoctoral Researcher Kasper Katisko, MD, PhD, kasper.katisko (a) uef.fi

Research Director, Adjunct Professor Annakaisa Haapasalo, annakaisa.haapasalo (a) uef.fi, https://uefconnect.uef.fi/en/person/annakaisa.haapasalo/

Research Director, Adjunct Professor Eino Solje, eino.solje (a) uef.fi, https://uefconnect.uef.fi/en/person/eino.solje/

Research article:

Katisko, K.*, Huber, N.*, Kokkola, T. et al. Serum total TDP-43 levels are decreased in frontotemporal dementia patients with C9orf72 repeat expansion or concomitant motoneuron disease phenotype. Alz Res Therapy 14, 151 (2022). https://doi.org/10.1186/s13195-022-01091-8. *Equal contribution.