Fig. 3: P-tau 181 and p-tau 217 immunoreactivity in muscle biopsies.

Immunohistochemical findings from a disease control (subject no. 8, male, 45 years old, diagnose: myalgia and cramps, disease duration 24 months, biopsy from biceps brachii, further details in Supplementary Table 6) and a patient with ALS (subject no. 4, male, 75 years old, disease duration 29 months, definite ALS according to the revised El Escorial criteria, King’s stage 4, biopsy from vastus lateralis, further details in Supplementary Table 6) are shown. Muscle biopsies from disease controls (n = 14) showed normal-sized, predominantly hexagonal fibres with random variations in muscle fibre size and shape. Conversely, biopsies from patients with ALS (n = 13) showed neurogenic features, including grouped or even fascicular atrophy, with small-angled fibres (example of atrophic fibre marked with white arrowhead) and nuclear bags, often accompanied by compensatory hypertrophy of unaffected fibres (black asterisk). Both ALS (n = 13) and disease control (n = 14) muscle biopsies showed p-tau 181 and p-tau 217 immunoreactivity (scale bar: 50 µm) predominantly localised to the myonuclei (black arrowheads), sometimes extending into the perinuclear regions. In all ALS samples, we found increased sarcoplasmic reactivity to p-tau181 and p-tau 217 in atrophic muscle fibres (white arrowhead), whereas normal or hypertrophic fibres did not show increased sarcoplasmic reactivity (black asterisk).