Serum neurofilament light protein as a biomarker across the cognitive decline continuum: a cross-sectional study from an Indian cohort

The Alzheimer’s disease (AD) continuum spans from healthy aging to subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. Serum Neurofilament Light Protein (NfL) is a potential non-invasive biomarker for neurodegeneration. This study evaluates serum NfL across the cognitive decline continuum in an Indian cohort. To assess serum NfL as a biomarker for early and progressive neurodegeneration, including its diagnostic utility in SCD, MCI, and AD. This case-control study included 129 participants: 28 cognitively normal older adults (HC), 32 with SCD, 33 with MCI, and 36 with AD. Serum NfL levels were measured using Simoa ® technology. The association of NfL with cognitive decline was analyzed using a Generalized Linear Model (GLM) adjusted for age and sex, and receiver operating characteristic (ROC) curves assessed diagnostic performance. Serum NfL median levels progressively increased across groups: HC (21.1 pg/mL), SCD (28.94 pg/mL), MCI (35.5 pg/mL), and AD (48.64 pg/mL). Compared to HC, NfL levels were significantly higher in SCD (adjusted coefficient: 0.59, p = 0.004), MCI (0.72, p = 0.001), and AD (1.13, p < 0.001). ROC analysis showed good discrimination: AUC was 0.795 for SCD vs. HC, 0.908 for MCI vs.HC, and 0.941 for AD vs. HC. The study demonstrates a clear association between rising serum NfL levels and advancing cognitive decline. Serum NfL demonstrated potential as a sensitive and non-invasive biomarker for early detection and staging of cognitive decline. The establishment of population-specific cut-offs within an Indian cohort contributes to global efforts toward standardizing blood-based biomarkers for AD.