Received on December 10, 2003
Accepted on June 1, 2004

Proteomics and Protein Markers

Brain- and Heart-Type Fatty Acid-Binding Proteins in the Brain: Tissue Distribution and Clinical Utility

¹ Departments of Molecular Genetics and Biophysics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
² Department of Biochemistry, University of Münster, Münster, Germany.
³ Departments of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands, and Molecular Genetics
⁴ Department of Psychiatry, University Hospital Maastricht, Maastricht, The Netherlands.
⁵ Department of Surgery, Medical Academy, Bialystok, Poland.
⁶ 2 Department of Biochemistry, University of Münster, Münster, Germany.
⁷ Department of Neurology, University Hospital Maastricht, Maastricht, The Netherlands.
⁸ Department of Biophysics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
⁹ Department of Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands.
¹⁰ Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

^* To whom correspondence should be addressed. E-mail: maurice.pelsers{at}gen.unimaas.nl.

Background: Detection of brain injury by serum markers is not a standard procedure in clinical practice, although several proteins, such as S100B, neuron-specific enolase (NSE), myelin basic protein, and glial fibrillary acidic protein, show promising results. We investigated the tissue distribution of brain- and heart-type fatty acid-binding proteins (B-FABP and H-FABP) in segments of the human brain and the potential of either protein to serve as plasma marker for diagnosis of brain injury.

Methods: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14). The protein markers S100B and NSE were measured for comparison. Reference values of B-FABP and H-FABP were established in healthy individuals (n = 92).

Results: The frontal, temporal, and occipital lobes, the striatum, the pons, and the cerebellum had different tissue concentrations of B-FABP and of H-FABP. B-FABP ranged from 0.8 µg/g wet weight in striatum tissue to 3.1 µg/g in frontal lobe. H-FABP was markedly higher, ranging from 16.2 µg/g wet weight in cerebellum tissue to 39.5 µg/g in pons. No B-FABP was detected in serum from healthy donors. H-FABP serum reference value was 6 µg/L. In the MTBI study, serum B-FABP was increased in 68% and H-FABP in 70% of patients compared with S100B (increased in 45%) and NSE (increased in 51% of patients). In ECT, serum B-FABP was increased in 6% of all samples (2 of 14 patients), whereas H-FABP was above its upper reference limit (6 µg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 µg/L) in 0.4% of all samples.

Conclusions: B-FABP and H-FABP patterns differ among brain tissues, with the highest concentrations in the frontal lobe and pons, respectively. However, in each part of the brain, the H-FABP concentration was at least 10 times higher than that of B-FABP. Patient studies indicate that B-FABP and H-FABP are more sensitive markers for minor brain injury than the currently used markers S100B and NSE.