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TDP-43 Accumulation Can Be Novel Diagnostic Characteristic For ALS Patients- New Study

Author: Medical Team (Alniche Life Sciences)

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A recent study published in Jama Open Network revealed that the accumulation of axonal pTDP-43 may be the novel diagnostic biomarker for patients with amyotrophic lateral sclerosis (ALS). The main objective of the study was to explore characteristic pathological hallmark present in the muscle tissues of patients suffering from amyotrophic lateral sclerosis.

Background:

One of the major aspects of the mechanism of amyotrophic lateral sclerosis(ALS) includes degeneration of neuromuscular connections and axons (ALS). The formation of ubiquitinated inclusions immunoreactive to transactive response DNA-binding protein 43 (TDP-43) is pathologically defined in the vast majority of amyotrophic lateral sclerosis patients. The study was composed of core parts: Retrospective population-based cohort comprising of one-year follow-up and Autopsy based case control portion. The autopsy based study consist of patients suffering from sporadic ALS (SALS) having TDP-43 pathology and inclusion of non-ALS control Patients.

Muscle tissues obtained from tongue, biceps branchii, rectus femoris, diaphragm, of Patients with autopsy gave confirmation of SALS whereas examination of patients without ALS was conducted through either paraffin embedded formalin fixed sections or sections frozen with liquid nitrogen or cooled isopentane. Histochemistry and Immunohistochemical analysis was conducted to confirm Pathological diagnosis. Time period for data collection was from September 2019 to June 2021.

Results of the study:

It was observed that a total of 10 patients with autopsy-confirmed Sporadic ALS with mean age 76.1 years at death, exhibited axonal phosphorylated TDP-43 (pTDP-43)- positive accumulations in intramuscular nerve bundles which was not seen in 12 control patients without ALS.

Out of the 114 patients with mean age 62.3 years, 71 patients i.e., 62.3 % exhibited intramuscular nerve bundles and 43 patients i.e., 37.7% did not.

Out of those patients who exhibited phosphorylated transactive response DNA-binding protein 43-positive intramuscular nerve bundles with mean age 62.5 years, 33 patients i.e., 66.7% were later diagnosed with the ALS.  Out of those patients without evident nerve bundles, 3 were later diagnosed with condition. Among the ALS patients in biopsy cohort, 9 patients with phosphorylated TDP-43 (pTDP-43)- positive bundles had only lower motor neuron symptoms.

Hence, Researchers of this study concluded that presence of axonal phosphorylated transactive response DNA-binding protein 43 accumulations in the intramuscular nerve bundles may be characteristic for patients with ALS and that it can be considered as a novel diagnostic biomarker for ALS.

Reference: Kurashige T, Morino H, Murao T, et al. TDP-43 Accumulation Within Intramuscular Nerve Bundles of Patients with Amyotrophic Lateral Sclerosis. JAMA Neurol. Published online May 23, 2022. doi:10.1001/jamaneurol.2022.1113