Biological significance of target fibres in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive disease characterised by degeneration of upper and lower motor neurons. The histological feature of skeletal muscles in ALS is the presence of denervated and reinnervated myofibres including small angulated fibres, grouped atrophy and fibre type grouping. Moreover, target/targetoid fibres (TFs) are frequently observed as abnormal structures of myofibres in ALS. A classic study revealed TFs in 50% of cases of biopsy-proven motor neuron diseases.1 The target fibre was first described as a sign of muscle fibre denervation in 1961.1 The name ‘target fibre’ is derived from its appearance on the transverse section that contains three more or less distinct concentric zones,1 and the central zone contains longitudinally oriented wavelike threads, possibly derived from Z-disc and bundles of myofilaments.2 The components of TFs have been identified as LC3, desmin, αB-crystallin, dystrophin, filamin C and Hsp27.2 However, the biological significance of TFs remains unclear. In contrast to the neuropathological changes in motor neurons that are assessable at autopsy, histological evaluation of skeletal muscles can be conducted before the death of the patients, which may contribute to diagnosis at an early-stage disease and evaluation of therapeutic efficacy. The present study aimed to determine the biological significance of the formation of TFs in neurogenic muscular atrophy in ALS. ### Patients and clinical assessments We retrospectively analysed the medical records of 17 consecutive patients with ALS who were admitted to the Department of Neurology, Kumamoto University Hospital, from January 2005 to December 2017, and who underwent muscle biopsy to exclude myopathies because they lacked upper motor neuron (UMN) signs and/or showed elevation of serum creatine kinase (CK) levels. We recorded the clinical characteristics as shown in online supplementary table 1. ### Supplementary data [jnnp-2020-324151supp001.pdf] ### Histological analyses Muscle biopsy samples had been examined by routine histochemical techniques including a series of myofibrillar adenosine triphosphatase …