Blood samples, PET imaging link brain injuries to chronic encephalopathy

2019 04 30 23 29 0302 Brain 400

Blood tests and positron emission tomography (PET) imaging with flortaucipir have correlated two key biomarkers of chronic traumatic encephalopathy (CTE) in military personnel who experienced traumatic brain injuries from blasts. Study results were published online on February 25 in Molecular Psychiatry.

Researchers observed elevated levels of tau tangles and a certain blood chemical associated with traumatic brain injury (TBI), both of which could indicate current or future acute brain degeneration and possible progression to CTE as a result of brain injury from an improvised explosive device (IED).

"These findings have implications for understanding the relationship of chronic blast-related injury to human neurodegenerative diseases including CTE," wrote first author Dara Dickstein, PhD, an adjunct assistant professor of neuroscience at Icahn School of Medicine at Mount Sinai, and colleagues. "The current data provide evidence ... to support the existence of a relationship involving blast injury and clinical neuropsychiatric syndromes."

It's estimated that 10% to 20% of veterans who served in Iraq and Afghanistan sustained mild TBI from IEDs and other explosions. While symptoms of mild TBI often dissipate within months of an incident, neurological deterioration and behavioral dysfunction can linger for years.

Two distinct chemical changes occur during neurodegeneration. One is the accumulation of tau neurofibrillary tangles, which are associated with the onset of dementia, Alzheimer's disease, and CTE. Through PET imaging, flortaucipir (Avid Radiopharmaceuticals) has been shown to bind to tau neurofibrillary tangles in postmortem brain tissue of patients with Alzheimer's disease.

The second change is the leakage of a protein known as neurofilament light (NfL) from the brain into the blood. Elevated levels of NfL are evident in patients with a variety of brain injuries, including mild TBI and neurodegenerative diseases.

To explore a connection between these factors, the researchers analyzed 10 veterans (mean age, 41.2 ± 9.4 years) who had at least one mild TBI and reported chronic behavioral issues and cognitive deficiencies. The cohort also included seven healthy, age-matched subjects. All 17 participants underwent 3-tesla structural magnetic resonance imaging (MRI) scans, followed by PET imaging with 370 MBq (10 mCi) of flortaucipir.

The researchers targeted six cortical brain regions -- the frontal, temporal, parietal, precuneus, anterior cingulate, and posterior cingulate cortex -- where tau protein is known to accumulate after a traumatic brain injury.

Levels of NfL in the blood were assessed using an ultrasensitive single-molecule array platform (Simoa, Quanterix), a digital form of an enzyme-linked immunosorbent assay (ELISA) that allows the detection of proteins at subfemtomolar concentrations.

The PET images revealed that five of the 10 veterans had excessive retention of flortaucipir at white/gray-matter junctions in the frontal, parietal, and temporal brain regions, which indicates tau accumulation and the likelihood of neurodegeneration. The researchers also observed elevated levels of NfL in the plasma of veterans displaying excess flortaucipir retention. As with tau accumulation, evidence of NfL could be an indication of neurodegenerative decline.

While the findings are not conclusive, they "support an emerging consensus" that NfL and other biomarkers could play an important role in monitoring postconcussive recovery and warrant additional research, the researchers concluded.

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