TDP-43 accumulation likely indicator for patients with ALS

Presence of axonal phosphorylated transactive response DNA-binding protein 43, or pTDP-43, accumulation in intramuscular nerve bundles is a likely biomarker for patients diagnosed with ALS, according to a study published in JAMA Neurology.

“The vast majority of [sporadic ALS (SALS)] cases are pathologically characterized by the deposition of abnormal ubiquinated inclusions immunoreactive to TDP-43,” Takashi Kurashige, MD, PhD, of the department of neurology, National Hospital Organization Kure Medical Center in Japan, and colleagues wrote.

Researchers sought to identify and characterize the histopathology of the TDP-43 axon in the skeletal muscle of patients with ALS.

The study was composed of two parts: a retrospective population-based cohort, which included 114 patients (mean age 62.3 years, 67% male) who underwent open muscle biopsy at Kure Medical Center from Jan. 1, 2004 to Sept. 30, 2019 with a minimum 1 year of follow-up, and a case-control portion, which included 10 patients diagnosed with SALS and TDP-43 pathology after postmortem muscle tissue examination, as well as 12 control participants with non-ALS diagnosis. Data were collected between September 2019 and June 2021 and then analyzed in June 2021.

Results showed, among 114 patients in the cohort study, 71 (62.3%) exhibited intramuscular nerve bundles. In those who exhibited pTDP-43-positive intramuscular nerve bundles, 33 patients (22 male, mean age, 65.2 years) were later diagnosed with ALS. The other 38 patients (26 male) showed no pTDP-43-positive bundles and did not develop ALS. Data additionally revealed that in patients lacking evident nerve bundles (28 male, mean age, 61.3 years), three were later diagnosed with ALS.

“Results of this dual case-control and cohort study suggest that axonal pTPD-42 accumulations may be characteristic for patients with ALS, and as a result, may be a novel diagnostic biomarker for ALS,” Kurashige and colleagues wrote.