Tracking the Plasma C-Terminal Agrin Fragment as a Biomarker of Neuromuscular Decline in 18-to 87-Year-Old Men

Objectives Plasma C-terminal agrin-fragment-22 (CAF22), a breakdown product of neuromuscular junction, is a potential biomarker of muscle loss. However, its levels from adolescence to octogenarians are unknown. Methods We evaluated young (18-34 years, n = 203), middle-aged (35-59 years, n = 163), and old men (60-87 years, n = 143) for CAF22, handgrip strength (HGS), appendicular skeletal-mass index (ASMI), and gait speed. Results We found an age-associated increase in CAF22 from young (100.9 +/- 29 pmol) to middle-aged (128.3 +/- 38.7 pmol) and older men (171.5 +/- 35.5 pmol) (all p<0.05). This was accompanied by a gradual reduction in HGS (37.7 +/- 6.1 kg, 30.2 +/- 5.2 kg, and 26.6 +/- 4.7 kg, for young, middle-aged, and old men, respectively), ASMI (8.02 +/- 1.02 kg/m(2), 7.65 +/- 0.92 kg/m(2), 6.87 +/- 0.93 kg/m2, for young, middle-aged, and old men, respectively), and gait speed (1.29 +/- 0.24 m/s, 1.05 +/- 0.16 m/s, and 0.81 +/- 0.13 m/s, for young, middle-aged, and old men, respectively). After adjustment for age, we found negative regressions of CAF22 with HGS (- 0.0574, p < 0.001) and gait speed (- 0.0162, p < 0.001) in the cumulative cohort. The receiver operating characteristics analysis revealed significant efficacy of plasma CAF22 in diagnosing muscle weakness (HGS < 27 kg) (middle-aged men; AUC = 0.731, 95% CI = 0.629-0.831, p < 0.001, Older men; AUC = 0.816, 95% CI = 0.761-0.833, p < 0.001), and low gait speed (0.8 m/s) (middle-aged men; AUC = 0.737, 95% CI = 0.602-0.871, p < 0.001, older men; AUC = 0.829, 95% CI = 0.772-0.886, p < 0.001), and a modest efficacy in diagnosing sarcopenia (middle-aged men; AUC = 0.701, 95% CI = 0.536-0.865, p = 0.032, older men; AUC = 0.822, 95% CI = 0.759-0.884, p < 0.001) in middle-aged and older men. Conclusion Altogether, CAF22 increases with advancing age and may be a reliable marker of muscle weakness and low gait speed.