Serum neurofilament light protein as a biomarker across the cognitive decline continuum: a cross-sectional study from an Indian cohort
4 affiliations
- 1Department of Geriatric Medicine National Centre of Aging All India Institute of Medical Sciences, New Delhi, India
- 2Department of Biophysics All India Institute of Medical Sciences, New Delhi, India
- 3Rajagiri Hospital, Kochi, Kerala India
- 4Artemis Hospital, Gurgaon, India
Abstract
Background: 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.
Aims: To assess serum NfL as a biomarker for early and progressive neurodegeneration, including its diagnostic utility in SCD, MCI, and AD.
Methods: 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.
Results: 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.
Discussion: The study demonstrates a clear association between rising serum NfL levels and advancing cognitive decline.
Conclusions: 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.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s40520-026-03381-9.
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BibTeX
@article{rao2026serum,
title = {{Serum neurofilament light protein as a biomarker across the cognitive decline continuum: a cross-sectional study from an Indian cohort}},
author = {Akshata Rao and Masroor Anwar and Abhijith R Rao and Bhawana Painkra and Sakthi Kiruthika and Sunil Kumar and Yudhishthir Yadav and Aparajit Ballav Dey and Sharmistha Dey and Prasun Chatterjee},
journal = {Aging Clinical and Experimental Research},
year = {2026},
month = jul,
doi = {10.1007/s40520-026-03381-9},
url = {https://doi.org/10.1007/s40520-026-03381-9},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Serum neurofilament light protein as a biomarker across the cognitive decline continuum: a cross-sectional study from an Indian cohort
AU - Akshata Rao
AU - Masroor Anwar
AU - Abhijith R Rao
AU - Bhawana Painkra
AU - Sakthi Kiruthika
AU - Sunil Kumar
AU - Yudhishthir Yadav
AU - Aparajit Ballav Dey
AU - Sharmistha Dey
AU - Prasun Chatterjee
PY - 2026
DA - 2026/07/30
JO - Aging Clinical and Experimental Research
DO - 10.1007/s40520-026-03381-9
UR - https://doi.org/10.1007/s40520-026-03381-9
AB - Background: 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. Aims: To assess serum NfL as a biomarker for early and progressive neurodegeneration, including its diagnostic utility in SCD, MCI, and AD. Methods: 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. Results: 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. Discussion: The study demonstrates a clear association between rising serum NfL levels and advancing cognitive decline. Conclusions: 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. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s40520-026-03381-9.
SN - 1594-0667
SN - 1720-8319
ER -