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October 2015

Biofluid Biomarkers of Mild Traumatic Brain Injury: Whither Plasma Tau

Author Affiliations
  • 1Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, Seattle, Washington
  • 2Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle
  • 3Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington
  • 4Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle
  • 5Department of Pathology, University of Washington School of Medicine, Seattle
JAMA Neurol. 2015;72(10):1103-1105. doi:10.1001/jamaneurol.2015.1789

The search for plasma biomarkers of mild traumatic brain injury (mTBI) remains intense. The US Department of Defense and US Department of Veterans Affairs have invested more than $100 million toward this effort and the General Electric National Football League Challenge award made to Quanterix and Banyan Biomarkers is an indicator of the continued enthusiasm for this approach to biomarker discovery despite the current meager returns.

A handful of plasma biomarkers, including s100β, glial fibrillary acidic protein, neuron-specific enolase, myelin basic protein, and ubiquitin C-terminal hydrolase–L1, have consistently demonstrated to be elevated in acute and more severe head trauma1-3 and are informative with respect to prognosis.1 A single study in boxers following a bout showed elevated serum neuron-specific enolase that persisted for 2 months.4 However, no plasma or serum biomarkers have previously been identified that are persistently elevated in mTBI long after exposure. Whether mTBI, particularly, repetitive mTBI, which has been termed the signature injury of the wars in Iraq and Afghanistan, puts service members and veterans at long-term risk of tauopathy-related neurodegeneration and dementia is an urgent concern that has heightened the need for biofluid biomarkers of tauopathy. The difficulty in identifying blood biomarkers in mTBI is understandable given that most, if not all, central nervous system–derived markers are in extremely low concentration when measured in plasma or serum. Therefore, investigators and funding agencies have hoped that development of the ultrahigh-sensitivity Quanterix Simoa technology will be a game changer for identifying blood biomarkers of mTBI.

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