Serum TDP-43 levels help identify common neuropathologic 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 prognosis is often challenging because the frontotemporal dementia spectrum includes several subtypes that differ in symptoms, genetics, and neuropathology, i.
e.
, disease-associated brain changes
.
Typically, the protein that accumulates in the brains of FTD patients and harms their neurons is either TDP-43 or tau protein
.
Understanding the neuropathological changes in patients already in the diagnostic phase is particularly helpful
in assessing their prognosis and possible future treatments.

A recent study by 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 that included all the most common subtypes
of the disease.
TDP-43 levels
were measured from patient blood samples using sensitive single molecule array (Simoa) technology.

The researchers found that patients with repeated amplification of C9orf72 or with motor neuron disease had significantly lower
serum TDP-43 levels.
Previous studies have shown that these patients typically accumulate the TDP-43 protein
in the brain.
Lower levels of TDP-43 were not observed in MAPT mutation carriers, who typically have tau protein accumulation
in their brains.

"Our current diagnostic methods are not sensitive or accurate enough to distinguish patients with TDP-43 neuropathology from those with other frontotemporal dementia
.
However, this study shows that TDP-43 is a potentially useful biomarker if more specific and sensitive assays can be developed," said
Dr.
Kasper Katisko, a postdoctoral researcher and co-first author at the University of Eastern Finland.

In the future, a simple blood sample is likely to be used to distinguish between the actual neuropathological subtypes of frontotemporal dementia and other forms of dementia
.
This will allow differential diagnosis to become increasingly rapid and accurate, allowing the development of patient-specific interventions
that affect disease progression.

The findings were published in
the journal Alzheimer's Research and Treatment.
The project is led
by Annakaisa Haapasalo, Research Director of the A.
I.
Virtanen Institute of Molecular Sciences, and Eino Solje, Research Director of the Institute of Clinical Medicine, University of Eastern Finland.