Peripheral plasma levels of the CNS protein tau are chronically elevated after traumatic brain injury and appear to correlate with the severity of postconcussive symptoms, according to a report published Aug. 3 in JAMA Neurology.
If these findings are confirmed, this will be the first biomarker that is sensitive and specific to persistent traumatic brain injury–related symptoms. The results also suggest that “months to years after the primary brain injury, there may be a continuation of secondary injuries with residual axonal degeneration and blood-brain barrier disruptions in this population that may contribute to the maintenance of postconcussive disorder symptoms and affect symptom severity,” wrote Anlys Olivera, Ph.D., of the National Institute of Nursing Research, Bethesda, Md., and her associates.
Tau is a protein that stabilizes the structure of the axonal cytoskeleton. It is elevated in the cerebrospinal fluid and the peripheral blood (albeit in extremely low concentrations) of patients with severe traumatic brain injury (TBI), professional boxers, and athletes who sustain concussions. The extremely low levels of tau in the peripheral blood have been very difficult to measure until the recent development of an ultrahigh-sensitivity immunoassay technology. Using this innovation, the researchers were able to examine for the first time the associations between plasma tau levels and the frequency and severity of deployment-related TBIs.
Over a 2-year period, Dr. Olivera and her associates assessed tau levels in 70 members of the military who self-reported one or more TBIs and 28 control subjects without TBI who were matched for age, sex, race, time since deployment, and number of deployments. Almost all of those in the TBI group had been injured at least 18 months previously. The most common sources of TBI were blows to the head, exposure to blasts, vehicular crashes, and sports-related concussions.
Total tau was significantly increased in the TBI group (mean level, 1.13 pg/mL), compared with the control group (0.63 pg/mL). Total tau also increased with increasing severity of the initial brain injury, with increasing numbers of TBIs, and increasing severity of present-day postconcussive symptoms. These associations, moreover, were independent of symptoms of posttraumatic brain disorder (PTSD) and depression, which were prevalent in the TBI group, the investigators said (JAMA Neurol. 2015 Aug 3 doi: 10.1001/jamaneurol.2015.1383).
Tau is not only a marker of brain injury; it also can contribute to secondary injury processes such as inflammation, which makes it a potential target for therapy. If the findings of this study are confirmed and extended to demonstrate a direct mechanistic relationship between TBI and tau aggregation, treatments such as the direct delivery of proteasomes “would be invaluable, considering the dearth of treatments for TBIs and chronic [postconcussive disorder] symptoms,” Dr. Olivera and her associates said.
Among the limitations cited by the investigators are lack of neuroimaging and neuropsychological data.
This study was supported by the National Institutes of Health’s National Institute of Nursing Research and the Center for Neuroscience and Regenerative Medicine, which is a collaborative program between the Department of Defense and the NIH. Dr. Olivera reported having no relevant financial disclosures. One of her associates reported ties to Quanterix, developer of the ultrahigh-sensitivity Simoa technology used in this study, which allows measurement of extremely low levels of tau and other CNS-derived biomarkers in the plasma or serum.