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Background <p>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.</p> Aims <p>To assess serum NfL as a biomarker for early and progressive neurodegeneration, including its diagnostic utility in SCD, MCI, and AD.</p> Methods <p>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<sup>®</sup> 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.</p> Results <p>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, <i>p</i> = 0.004), MCI (0.72, <i>p</i> = 0.001), and AD (1.13, <i>p</i> &lt; 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.</p> Discussion <p>The study demonstrates a clear association between rising serum NfL levels and advancing cognitive decline.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月30日

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  • Akshata Rao,
  • Masroor Anwar,
  • Abhijith R Rao,
  • Bhawana Painkra,
  • Sakthi Kiruthika,
  • Sunil Kumar,
  • Yudhishthir Yadav,
  • Aparajit Ballav Dey,
  • Sharmistha Dey,
  • Prasun Chatterjee

摘要

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.