Validating serum S100B and neuron-specific enolase as biomarkers for the human brain - a combined serum, gene expression and MRI study.
BACKGROUND
Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE) is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now.


METHODS
We acquired two magnetic resonance imaging parameters sensitive to changes in gray and white matter (T(1)-weighted/diffusion tensor imaging) and obtained serum S100B and NSE levels of 41 healthy subjects. Additionally, we analyzed whole brain gene expressions of S100B in another male cohort of three subjects using the Allen Brain Atlas. Furthermore, a female post mortal brain was investigated using double immunofluorescence labelling with oligodendrocyte markers.


RESULTS
We show that S100B is specifically related to white matter structures, namely the corpus callosum, anterior forceps and superior longitudinal fasciculus in female subjects. This effect was observed in fractional anisotropy and radial diffusivity - the latest an indicator of myelin changes. Histological data confirmed a co-localization of S100B with oligodendrocyte markers in the human corpus callosum. S100B was most abundantly expressed in the corpus callosum according to the whole genome Allen Human Brain Atlas. In addition, NSE was related to gray matter structures, namely the amygdala. This effect was detected across sexes.


CONCLUSIONS
Our data demonstrates a very high S100B expression in white matter tracts, in particular in human corpus callosum. Our study is the first in vivo study validating the specificity of the glial marker S100B for the human brain, and supporting the assumption that radial diffusivity represents a myelin marker. Our results open a new perspective for future studies investigating major neuropsychiatric disorders.
Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. paolo@cbs.mpg.de
Daniel-Paolo
DP
Streitbürger
Katrin
K
Arelin
Jürgen
J
Kratzsch
Joachim
J
Thiery
Johann
J
Steiner
Arno
A
Villringer
Karsten
K
Mueller
Matthias L
ML
Schroeter
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D010751:Phosphopyruvate Hydratase