Association between neurofilament light chain, glial fibrillary acidic protein, and sarcopenia in older Indian adults: evidence from LASI-DAD

Abstract Background Sarcopenia, the age-related loss of muscle mass and strength, is a leading cause of disability and frailty in older adults. Though primarily seen as a musculoskeletal condition, emerging evidence suggests a role for neurodegenerative mechanisms such as axonal loss and neuroinflammation. Circulating biomarkers like glial fibrillary acidic protein (GFAP), reflecting astrocyte activation, and neurofilament light chain (NfL), indicating axonal injury, may signal subclinical neurological dysfunction. This study examined associations between plasma GFAP and NfL levels and the presence and severity of sarcopenia in older Indian adults using data from the nationally representative Longitudinal Aging Study in India–Diagnostic Assessment of Dementia (LASI-DAD) cohort. Methods We used data from the Longitudinal Aging Study in India–Diagnostic Assessment of Dementia (LASI-DAD), a nationally representative sample of older adults aged ≥ 60 years. Sarcopenia was classified using Asian Working Group for Sarcopenia (AWGS) 2019 criteria based on handgrip strength, gait speed, and calf circumference, and categorized into no sarcopenia, sarcopenia, and severe sarcopenia. Plasma levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were quantified using Simoa® HDX platform. Results We analyzed 1,429 community-dwelling older adults; 53.1% had sarcopenia and 38.6% had severe sarcopenia. Median plasma GFAP levels increased from 99.6 pg/mL (IQR: 70.2–140.9) in those without sarcopenia to 122.4 pg/mL (IQR: 84.0–181.6) in sarcopenia and 158.1 pg/mL (IQR: 101.4–228.4) in severe sarcopenia (p < 0.001). Similarly, median NfL levels were 20.5 pg/mL (IQR: 15.8–29.4), 29.1 pg/mL (IQR: 19.8–44.6), and 37.6 pg/mL (IQR: 25.0–59.2), respectively (p < 0.001). In fully adjusted models, higher GFAP levels were associated with sarcopenia (RRR: 1.23; 95% CI: 1.04–1.45; p = 0.014) and severe sarcopenia (RRR: 1.48; 95% CI: 1.19–1.83; p < 0.001). NfL was associated with sarcopenia (RRR: 1.37; 95% CI: 1.16–1.61; p < 0.001) and severe sarcopenia (RRR: 2.01; 95% CI: 1.56–2.58; p < 0.001). Conclusion Elevated GFAP and NfL were independently associated with greater sarcopenia severity, suggesting neurodegenerative involvement in sarcopenia among older Indian adults. These biomarkers may offer valuable insights into the neural contributions to muscle decline in aging populations and could support future risk stratification and early intervention strategies.