Table 1.

Potential fluid biomarkers of mild TBI

Marker	Process or structure affected	Research findings in mild TBI
		Cerebrospinal fluid	Blood
Cerebrospinal fuid:serum albumin ratio	Blood–brain barrier	Detection method not sensitive enough to changes in concentration53,54	NA
Interleukins and other acute-phase infammatory response proteins	Neuroinfammation	NA	NA
Total tau protein	Axon	Levels peak 4–10 days after injury54,71	Elevated levels in hypoxic brain injury;101,102 studies in mild TBI are lacking
Myelin basic protein	Axon	NA	Detection methods not sensitive in mild TBI79
Neuroflament light polypeptide	Axon	Levels peak 4–10 days after injury54,71	NA
Neuroflament heavy polypeptide	Axon	NA	NA
γ-Enolase	Neuron	Levels confounded by lysis of red blood cells in blood-contaminated cerebrospinal fuid82	Serum levels very sensitive to lysis of red blood cells in blood-contaminated cerebrospinal fuid82
S100-B	Astroglial cells	Levels are elevated, but a less sensitive marker than tau protein and neuroflaments71	Results may be confounded by release from extracerebral tissues77
Glial fbrillary acidic protein	Astroglial cells	Elevated levels, but a less sensitive marker than tau and neuroflament proteins54,71	Serum levels correlate with changes on brain imaging;118 extracerebral protein has not been detected74
Secreted APP-α and APP-β	Axon	NA	NA
Amyloid-β40 and amyloid-β42	Plaque pathology	No change in levels57,74	NA
Spectrin breakdown products	Neuron	NA	NA
Ubiquitin carboxyl-terminal hydrolase isoenzyme L1	Neuron	NA	One pilot study showed promising results123
Peripheral blood mononuclear small noncoding RNA molecules	Unknown	NA	One pilot study suggests altered expression of three RNA molecules in mild-TBI-exposed military personnel125

Abbreviations: APP, amyloid precursor protein; NA, not available; TBI, traumatic brain injury.