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<p>The diagnosis of Alzheimer’s disease (AD) has transitioned from a clinical to a clinical-biological framework, with biomarkers playing a crucial role in diagnosis and patient stratification. This retrospective study aimed to: evaluate correlations between neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and transactive response DNA-binding protein 43&#xa0;kDa (TDP-43) levels in CSF and serum (measured via SIMOA) in AD patients; compare serum levels with healthy controls (HCs); analyze relationships with core AD biomarkers; and explore associations with cognitive impairment. Serum NfL and GFAP levels were significantly elevated in AD patients compared to HCs (<i>p</i> &lt; 0.001). Strong positive correlations were observed between CSF and serum levels for both NfL (<i>p</i> &lt; 0.001) and GFAP (<i>p</i> &lt; 0.001). CSF NfL correlated with CSF GFAP (<i>p</i> &lt; 0.001), while serum NfL correlated with serum GFAP (<i>p</i> &lt; 0.001) and CSF GFAP (<i>p</i> = 0.006). Both CSF NfL (<i>r</i> = 0.3, <i>p</i> = 0.02) and serum NfL (<i>r</i> = 0.3, <i>p</i> = 0.008) positively correlated with age (<i>p</i> = 0.01). Passing–Bablok regression revealed slopes of 0.01 for NfL and 0.02 for GFAP. Regression models demonstrated high diagnostic accuracy for NfL (specificity/sensitivity: 81%/82%) and GFAP (90%/92%). No significant differences were found in serum TDP-43 levels between AD patients and HCs, nor were correlations observed with other biomarkers and age. A negative correlation was detected between pTau/Aβ 1–42 ratio and MMSE scores (<i>p</i> &lt; 0.02). In conclusion, serum NfL and GFAP exhibit moderate correlations with their CSF counterparts in AD, supporting their potential as less invasive surrogate biomarkers. While serum NfL and GFAP effectively discriminate AD from HCs, serum TDP-43 lacks comparable diagnostic utility.</p>

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Comparison of TDP-43, NfL, and GFAP in cerebrospinal fluid and serum in Alzheimer’s disease

  • 期刊论文

  • 发表日期：

    2026年4月24日

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  • Carlo Manco,
  • Delia Righi,
  • Alessio Rocco Sangiorgio,
  • Barbara Pucci,
  • Nicola De Stefano,
  • Domenico Plantone

摘要

The diagnosis of Alzheimer’s disease (AD) has transitioned from a clinical to a clinical-biological framework, with biomarkers playing a crucial role in diagnosis and patient stratification. This retrospective study aimed to: evaluate correlations between neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and transactive response DNA-binding protein 43 kDa (TDP-43) levels in CSF and serum (measured via SIMOA) in AD patients; compare serum levels with healthy controls (HCs); analyze relationships with core AD biomarkers; and explore associations with cognitive impairment. Serum NfL and GFAP levels were significantly elevated in AD patients compared to HCs (p < 0.001). Strong positive correlations were observed between CSF and serum levels for both NfL (p < 0.001) and GFAP (p < 0.001). CSF NfL correlated with CSF GFAP (p < 0.001), while serum NfL correlated with serum GFAP (p < 0.001) and CSF GFAP (p = 0.006). Both CSF NfL (r = 0.3, p = 0.02) and serum NfL (r = 0.3, p = 0.008) positively correlated with age (p = 0.01). Passing–Bablok regression revealed slopes of 0.01 for NfL and 0.02 for GFAP. Regression models demonstrated high diagnostic accuracy for NfL (specificity/sensitivity: 81%/82%) and GFAP (90%/92%). No significant differences were found in serum TDP-43 levels between AD patients and HCs, nor were correlations observed with other biomarkers and age. A negative correlation was detected between pTau/Aβ 1–42 ratio and MMSE scores (p < 0.02). In conclusion, serum NfL and GFAP exhibit moderate correlations with their CSF counterparts in AD, supporting their potential as less invasive surrogate biomarkers. While serum NfL and GFAP effectively discriminate AD from HCs, serum TDP-43 lacks comparable diagnostic utility.