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

Abstract

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 Three hundred adults aged between 50 and 83 years participated to this study (male participants, n = 150; mean age: 64.2 ± 8.7 years and female participants, 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 Neurofilament light chain levels were associated with grip strength and SMI (P = 0.005 and P = 0.045, respectively) and were significantly elevated in sarcopenic individuals, compared with non-sarcopenic participants (P < 0.001). Individuals with pre-sarcopenia (either low grip strength or low SMI) had significantly higher NfL levels, compared with healthy controls (P = 0.001 and P = 0.006, respectively). Male participants with either low grip strength or low SMI had significantly raised NfL levels (P = 0.006 and P = 0.002, respectively), while in female participants, NfL concentrations were significantly elevated only in those with low grip strength (P = 0.049). NfL concentration displayed acceptable diagnostic accuracy for sarcopenia (area under the curve = 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.

Effects of short‐term unloading and active recovery on human motor unit properties, neuromuscular junction transmission and transcriptomic profile

“…Single molecule array (SIMOA) analysis was also performed to evaluate neurofilament light chain concentration, a well‐established biomarker of axonal damage, previously employed both in aging and neurological disorders scenarios (Khalil et al., 2018 ; Pratt et al., 2022 ). The samples were submitted to the SIMOA service offered by Wieslab AB (a Svar Life Sci company, Lundavägen, Malmo, Sweden) in accordance with Good Laboratory Practice (GLP) principles.…”

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskel

“…First, we already discussed the D3-Cr dilution test and CAF measurement for which clinical data are convincing, but we do not have the appropriate technology to ensure widely available and accurate measurement for pharmacological trials. Additionally, apelin [ 149 ] and fibroblast growth factor-21 (FGF-21) [ 150 ] as musculoskeletal markers, together with neurofilament light chains (NfL) for the neuromuscular junction [ 151 ], have been identified as promising biochemical markers with clinically relevant data but with a too restricted number of studies to recommend their use in clinical trials. Finally, in the future, innovative approaches such as miRNA panels [ 152 ] and microbiome analysis [ 153 , 154 ] will probably find a place in the biochemical marker field, but it is certainly premature to define their clinical utility at the present time in sarcopenia.…”

Effects of a 2‐year exercise training on neuromuscular system health in older individuals with low muscle function

“…Other reports showed an increase in NfL with age 9,10 and negative correlations of this biomarker with physical performance, 11 suggesting a link between this phenomenon and the ongoing neuromuscular degeneration that is known to accompany ageing 2,6 . A very recent study reported higher NfL concentrations in sarcopenic than in pre‐sarcopenic and non‐sarcopenic older individuals, suggesting that the neuronal degeneration underlying sarcopenia development may be reflected in higher NfL serum concentrations 12 …”

“…2,6 A very recent study reported higher NfL concentrations in sarcopenic than in pre-sarcopenic and non-sarcopenic older individuals, suggesting that the neuronal degeneration underlying sarcopenia development may be reflected in higher NfL serum concentrations. 12 The stability of NMJs can be investigated by measuring the serum concentration of CAF, the 22-KDa C-terminal fragment of the protein agrin, which is a heparan-sulphate proteoglycan that stabilizes synaptic structures by aggregating acetylcholine receptors 13 and is irreversibly inactivated by the enzyme neurotrypsin. Upon agrin cleavage at the synaptic cleft, CAF is released in the circulation, with a consequent destabilization of the NMJ through degeneration of its endplate.…”