Many might think that it would be obvious to see if someone is suffering from traumatic brain injury (TBI), but the symptoms and resulting pathologies are often far more subtle than one might think. Consequently, TBI is often misdiagnosed or missed altogether. In fact, it's is the leading cause of death in the United States, and around 2.5 million people are diagnosed with it every year.
Repetitive mild TBI, often seen in contact sports, and single severe TBI, like with military blasts, can cause long lasting progressive neurological damage, such as chronic traumatic encephalopathy (CTE), which might not show until years down the line.
CTE is caused by a build-up in the brain of a misfolded protein called tau, and has many similarities to Alzheimer’s, the development of which is also associated with this protein. It is thought that while the cause is the same, the differences are in how the diseases manifest. Now, researchers at Harvard Medical School have been able prevent the build-up of this protein in mice that have suffered TBI, and hope that it could also be applied to those suffering with Alzheimer’s.
In healthy brains, the protein tau is involved with the internal scaffolding of cells, specifically in neurons. Tau normally exists in its “trans” form, but when misfolded forms what’s called “cis-tau.” It is this form of the protein, no longer able to perform its normal task, which contributes to both CTE and Alzheimer’s. The researchers were able to create two antibodies that could reliably distinguish between the cis and trans forms of tau, and prevent the development of CTE by the misshapen proteins.
The research, published in Nature Neuroscience, showed how TBI can induce CTE and the build-up of cis-tau in the brains of mice, and that while after mild trauma these levels started to drop, after severe trauma the levels persisted. They were also able to show how cis-tau starts to spread through the brains of the mice over a period of 6 months, and that the protein was causing apoptosis, or cell death, leading to further neurological damage.
When the mice were given the corresponding antibody, however, the researchers found that the cis-tau proteins – but importantly not trans-tau – were blocked from spreading and causing cell death, preventing the development of neurological damage and reversing the pathologies often associated with TBI. The researchers, who have also shown a direct link between CTE and Alzheimer’s, hope that this might prove useful in prevention and therapy for those suffering from the devastating disease.
Image in text: Neurons grown in tissue culture show tau protein stained red inside the cells. Credit: GerryShaw/Wikimedia Commons.
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