Significantly increased levels of the protein TDP-43 in the epidermis and in the cytoplasm of dermal cells may offer a biomarker for amyotrophic lateral sclerosis (ALS), according to a study published in the journal Cells.

The finding stems from an analysis of skin biopsies from 64 people: 44 had ALS, 10 had Parkinson disease or multiple sclerosis and served as neurological control subjects, and 10 were healthy control subjects. Researchers were interested if alterations in the cellular localization of cutaneous TDP-43 differed in people with ALS and could potentially serve as an early diagnostic marker. Current diagnosis is based on clinical symptoms after significant motoneuron degeneration has occurred, they explained.

According to the study, the number of skin cells with TDP-43 outside the cell nucleus in the cytoplasm was elevated in participants with ALS. It was already known that TDP-43 has abandoned the nucleus of motor neurons of the brain and spinal cord in 97% of patients with the disease; the study showed the same abnormality occurred in skin cells of participants in the ALS group but not in the control groups.

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“In the skin layers analyzed,” explained lead author Miguel Ángel Rubio of the Hospital del Mar and the Autonomous University of Barcelona in Spain, “the ALS patients presented more fibroblasts, which are basic tissue cells in the dermis, with the mark of the disease, which is normally seen in the spinal cord and the motor cortex, when compared with the members of the healthy control group and the control group with other pathologies.”

In skin samples taken from participants with ALS a year later, the abnormality persisted.

Specifically, the anomaly occurred in 24.1% of fibroblast cells of patients with ALS but was nearly nondetectable in healthy and neurological control subjects.

“We have a biomarker that works as a fingerprint of the disorder in the nervous system, and we also confirmed that it can be found in the skin,” Dr Rubio said. “Moreover, we can quantify and determine the theoretical cutoff point to be able to give a diagnosis in specific cases.”

The biomarker could help in situations of difficult diagnosis or in people with a family history of ALS, he noted. Further studies involving more patients are needed, however, to confirm the utility of the marker.

“It is probable that this marker, in presymptomatic stages, before having any initial motor manifestations, could already be present,” he added, “and that is why it may be relevant for a diagnosis.”

References

Rubio MA, Herrando-Grabulosa M, Velasco R, Blasco I, Povedano M, Navarro X. TDP-43 cytoplasmic translocation in the skin fibroblasts of ALS patients. Cells. Published online January 8, 2022. doi: 10.3390/cells11020209

Study of skin biopsies offers potential as new diagnostic marker for amyotrophic lateral sclerosis (ALS). New release. Universitat Autonoma de Barcelona. March 24, 2022. Accessed April 19, 2022.