Increased Serum NSE and S100B Indicate Neuronal and Glial Alterations in Subjects Under 71 Years With Mild Neurocognitive Disorder/Mild Cognitive Impairment

Maryna Polyakova; Karsten Mueller; Katrin Arelin; Leonie Lampe; Francisca S Rodriguez; Tobias Luck; Jürgen Kratzsch; Karl-Titus Hoffmann; Steffi Riedel-Heller; Arno Villringer; Peter Schoenknecht; Matthias L Schroeter

doi:10.3389/fncel.2022.788150

Increased Serum NSE and S100B Indicate Neuronal and Glial Alterations in Subjects Under 71 Years With Mild Neurocognitive Disorder/Mild Cognitive Impairment

Front Cell Neurosci. 2022 Jul 14:16:788150. doi: 10.3389/fncel.2022.788150. eCollection 2022.

Authors

Maryna Polyakova^{1

2

3

4}, Karsten Mueller¹, Katrin Arelin^{1

3}, Leonie Lampe^{1

3}, Francisca S Rodriguez^{3

5}, Tobias Luck^{3

6}, Jürgen Kratzsch^{3

7}, Karl-Titus Hoffmann⁸, Steffi Riedel-Heller^{3

9}, Arno Villringer^{1

3

8}, Peter Schoenknecht^{3

4

10}, Matthias L Schroeter^{1

2

3}

Affiliations

¹ Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
² Clinic for Cognitive Neurology, University of Leipzig, Leipzig, Germany.
³ LIFE-Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig, Germany.
⁴ University Clinic for Psychiatry and Psychotherapy, Leipzig University, Leipzig, Germany.
⁵ Research Group Psychosocial Epidemiology and Public Health, German Center for Neurodegenerative Diseases (DZNE), Greifswald, Germany.
⁶ Faculty of Applied Social Sciences, University of Applied Sciences Erfurt, Erfurt, Germany.
⁷ Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, Leipzig, Germany.
⁸ Institute of Neuroradiology, University Clinic, Leipzig, Germany.
⁹ Institute of Social Medicine, Occupational Health and Public Health (ISAP), Leipzig University, Leipzig, Germany.
¹⁰ Department of Psychiatry and Psychotherapy, University Affiliated Hospital Arnsdorf, Technical University of Dresden, Dresden, Germany.

Abstract

Background: Mild cognitive impairment (MCI) is considered a pre-stage of different dementia syndromes. Despite diagnostic criteria refined by DSM-5 and a new term for MCI - "mild neurocognitive disorder" (mild NCD) - this diagnosis is still based on clinical criteria.

Methods: To link mild NCD to the underlying pathophysiology we assessed the degree of white matter hyperintensities (WMH) in the brain and peripheral biomarkers for neuronal integrity (neuron-specific enolase, NSE), plasticity (brain-derived neurotrophic factor, BDNF), and glial function (S100B) in 158 community-dwelling subjects with mild NCD and 82 healthy controls. All participants (63-79 years old) were selected from the Leipzig-population-based study of adults (LIFE).

Results: Serum S100B levels were increased in mild NCD in comparison to controls (p = 0.007). Serum NSE levels were also increased but remained non-significant after Bonferroni-Holm correction (p = 0.04). Furthermore, age by group interaction was significant for S100B. In an age-stratified sub-analysis, NSE and S100B were higher in younger subjects with mild NCD below 71 years of age. Some effects were inconsistent after controlling for potentially confounding factors. The discriminatory power of the two biomarkers NSE and S100B was insufficient to establish a pathologic threshold for mild NCD. In subjects with mild NCD, WMH load correlated with serum NSE levels (r = 0.20, p = 0.01), independently of age.

Conclusion: Our findings might indicate the presence of neuronal (NSE) and glial (S100B) injury in mild NCD. Future studies need to investigate whether younger subjects with mild NCD with increased biomarker levels are at risk of developing major NCD.

Keywords: BDNF; Brain-Derived Neurotrophic Factor; NSE; S100B; mild cognitive impairment; neuron-specific enolase; white matter hyperintensities.