Repetitive mild traumatic brain injury (mTBI) results in tau accumulation that is detectable with PET imaging, according to a new study published in Molecular Psychiatry. The findings raise the possibility that chronic traumatic encephalopathy (CTE) could be diagnosed during life.

Individuals who experience multiple mTBIs, such as those caused by shockwaves from blast explosions, can develop memory loss and alterations in mood or personality years after the initial injury. These symptoms can be a sign of the neurodegenerative disease CTE, which is characterized by aggregation of hyperphosphorylated tau in the brain. Currently, CTE can only be confirmed post mortem, but the aim of the new study, led by Gregory Elder and Sam Gandy, was to develop biomarkers to detect CTE in living individuals and perhaps guide therapeutic intervention.

“There are many young, otherwise-healthy military veterans who have suffered blast-related TBIs, some of them years in the past, who either aren’t getting better or, in some cases, are getting worse,” notes Elder. “We don’t know why or how to identify those at greatest risk.”

The researchers exposed rats to mTBI once per day for three consecutive days and analysed brain samples taken at 6 and 10 months after the last injury. The level of phosphorylated tau was higher in mTBI-exposed rats than in control rats at both timepoints, showing that tau pathology can be detected long after injury.

The researchers also performed brain imaging with the tau PET ligand 18F-AV1451 in ten veterans with histories of repeated blast exposure and symptoms of CTE and seven healthy controls. Excess ligand retention was observed in five of the veterans and none of the controls, suggesting that this approach can identify blast-induced tau pathology in humans. The pattern of ligand retention in the veterans resembled the post-mortem tau pathology usually seen in individuals with CTE.

Excess ligand retention was observed in five of the veterans

The researchers also measured blood levels of neurofilament light chain (NfL), which has been used as a biomarker of neurodegeneration, in the veterans and controls. No difference was observed between the two groups, but among the veterans, excess 18F-AV1451 retention was associated with higher NfL levels. “Next we are keen to see whether 18F-AV1451 and/or NfL can be used to predict which patients benefit from a new drug that relieves symptoms in blast-exposed rats,” concludes Gandy.