Biomarkers of disease may reflect tissue damage or disease mechanisms – that is, the pathophysiology of the condition. For many years, neurological diseases could only be described in clinical or neuropathological terms. However, in the last decade, we have come to understand some of the mechanisms underlying some of those diseases associated with the most severe morbidity and mortality – particularly Alzheimer's disease, multiple sclerosis (MS) and Parkinson's disease. In addition, we are increasingly recognizing substances which appear to be specific to the cells found in the brain which could act as biomarkers. Examples include N-acetylaspartate (in neurones), neurone-specific enolase (NSE) and an isoform of S-100 protein found in glial cells.

However, despite these advances, the application of biomarkers to neurodegenerative diseases has not been as easy as it has been for disorders of other tissues – notably, the heart, liver and skeletal muscle. Two major reasons exist for this: firstly, the presence of the blood–brain barrier and, secondly, the relatively small size of the adult brain (2% of body weight) as compared with the rest of the body and the systemic circulation. The former, therefore, impedes the loss of markers from the brain into the bloodstream while the relatively large size of the systemic circulation acts to dilute any marker released. In (pre)term infants, the brain as a proportion of total body weight (13%) is much larger than that of adults and the blood–brain barrier less well developed.