A biomarker is an objectively measured and evaluated characteristic which is an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention (Group,2001). Physicians in clinical practice routinely use biomarkers to diagnose and assess disease severity, assist in disease prognosis, and evaluate treatment efficacy. Generally, injury and/or cell death results in increased concentrations of a given biomarker, either due to the release of that biomarker from the injured cell (e.g. creatine phosphokinase (CPK) in patients with myocardial infarction) or the lack of excretion of a normally excreted chemical which results in its accumulation (e.g. blood urea nitrogen in patients with renal failure). In some cases, however, a decrease in biomarker concentrations indicates pathology (e.g. haptoglobin in patients with hemolytic anemia).

Development of a clinically acceptable “brain” biomarker has proven much more difficult than the development of biomarkers for other organs. The difficulty is likely due to a combination of anatomic, physiologic, and technical issues. The complexity of the brain and the concomitant complexity of its response to injury have been barriers to development of sensitive and specific brain biomarkers. The presence of the blood–brain barrier which limits the amount and size of the biomarkers that can cross into the serum has also been an important issue. Until recently, technical difficulties had hindered the ability to identify novel candidate biomarkers using proteomics and, as a result, the number of potential biomarkers has been limited.