Plasma neurofilament light levels associate with muscle mass and strength in middleaged and older adults: findings from GenoFit

Background Efforts to enhance diagnostic measures for sarcopenia have led to an increased focus on the screening utility of blood-based biomarkers. In this regard, circulating neurofilament light chain (NfL) levels are a potent indicator of axonal damage and have been linked with several neurological disorders. However, despite the strong neurogenic contribution to skeletal muscle health, no studies have explored the relevance of NfL concentrations to sarcopenia. With that in mind, this study aimed to examine the association between plasma NfL concentration and sarcopenic domains. Methods 300 adults aged between 50-83 years participated to this study (males, n=150; mean age: 64.2±8.7 years and females, n=150; mean age: 63.9±8.3 years). Body composition was assessed using dual-energy x- ray absorptiometry, and a skeletal muscle index (SMI) was calculated. Muscle strength was assessed with hand dynamometry. Sarcopenia was classified using the European Working Group on Sarcopenia in Older People criteria. Plasma NfL concentration was determined using a highly sensitive, enzyme- linked immunosorbent assay. Results NfL levels were associated with grip strength and skeletal muscle index (SMI) (p=0.005, p=0.045, respectively) and were significantly elevated in sarcopenic individuals, compared to non-sarcopenic participants (p<0.001). Individuals with pre-sarcopenia (either low grip strength or low SMI) had significantly higher NfL levels, compared to healthy controls (p=0.001, p=0.006, respectively). Males with either low grip strength or low SMI had significantly raised NfL levels (p=0.006, p=0.002, respectively), while in females, NfL concentrations were significantly elevated only in those with low grip strength (p=0.049). NfL concentration displayed acceptable diagnostic accuracy for sarcopenia (AUC=0.726, p<0.001). Conclusions Our study clearly demonstrates the indicative pertinence of circulating NfL levels to sarcopenic domains, supporting its potential use as a biomarker of sarcopenia. More studies are needed, however, to further illuminate the diagnostic value of circulating NfL. Future research should explore whether NfL levels are more powerfully linked with muscle strength than mass, and whether sex mediates the relevance of NfL concentrations to sarcopenic phenotypes.