Researchers link traumatic brain injury to a toxic form of the tau protein
Scientists at the University of Texas Medical Branch at Galveston (UTMB) have identified a molecular process that may help explain how traumatic brain injury (TBI) causes lasting neurological harm. Their work focuses on an abnormal assembly of the tau protein—known as tau oligomers—that is increasingly implicated in neurodegenerative disease.
Under normal conditions, tau is a vital protein that supports neuronal structure and function. However, in neurodegenerative disorders such as Alzheimer’s disease, tau can misfold and aggregate into different forms. One well-known aggregate is the neurofibrillary tangle, while another is a smaller, soluble assembly made of two to several tau molecules, referred to as tau oligomers. Evidence from multiple labs indicates that the oligomeric form is particularly toxic to nerve cells and may drive progressive dysfunction.
In controlled laboratory experiments using nontransgenic rats, UTMB researchers applied newly developed antibodies to detect and isolate tau oligomers following experimental brain injury. Remarkably, toxic tau oligomers appeared within four hours of injury and remained detectable for at least two weeks—suggesting a window during which these assemblies could initiate or amplify damage that lasts well beyond the initial trauma.
Using normal rats—rather than genetically modified models that overproduce abnormal tau—adds translational relevance to the findings. Because the animals did not carry engineered mutations, the rapid emergence of oligomeric tau after injury strengthens the possibility that similar processes occur in people after TBI and could contribute to later cognitive and neurological problems.
Lead author Bridget Hawkins, publishing with colleagues in the Journal of Biological Chemistry, emphasized the importance of measuring oligomers specifically. “While other teams have examined neurofibrillary tangles after TBI, we used an antibody that discriminates oligomers from total tau,” she stated. “That allowed us to show that a significant fraction of tau becomes the toxic oligomeric form after injury—enough to plausibly influence outcomes after TBI.”
The clinical relevance of tau oligomers is underscored by prior UTMB studies linking these assemblies to memory impairment. Long-term complications commonly associated with TBI—such as memory loss, seizures and disruption of sleep-wake cycles—could in part reflect the effects of persistent tau oligomers on neuronal circuits. The UTMB team proposes that interrupting oligomer formation may therefore reduce or prevent some of these chronic consequences.
One therapeutic strategy under consideration is antibody-based intervention. The same antibodies used in this research to label and study oligomers were developed during an effort to create immunotherapies for tau-related neurodegeneration. Those antibodies can selectively bind oligomeric tau without disrupting the normal function of healthy tau, offering a targeted approach for neutralizing the toxic species.
Senior author Rakez Kayed noted that the work is an early step toward therapy development: “We can target tau oligomers specifically in animal models, and the next phase is to optimize and humanize these antibodies with the aim of moving to clinical testing.” The researchers stress that additional studies will be needed to evaluate safety, dosing and whether antibody treatments can indeed prevent long-term deficits after TBI.
Research team, funding and publication details
The study’s authors include Bridget E. Hawkins (lead author), Shashirekha Krishnamurthy, Urmi Sengupta, Diana L. Castillo-Carranza, Donald S. Prough, George R. Jackson, Douglas S. DeWitt and Rakez Kayed. Funding and support for the work were provided by the Cullen Family Trust for Health Care, the Mitchell Center for Neurodegenerative Diseases, and the Moody Center for Traumatic Brain and Spinal Cord Injury Research/Mission Connect.
Contact: Jim Kelly – UTMB Galveston
Source: UTMB Galveston press release
Image Source: Brain scan image credited to NICHD/NIH (public domain).
Original Research: The full open-access article is available in the Journal of Biological Chemistry: “Rapid Accumulation of Endogenous Tau Oligomers in a Rat Model of Traumatic Brain Injury: Possible Link Between TBI and Sporadic Tauopathies,” by Hawkins et al.