Soldiers show prolonged elevations in protein linked to Alzheimer’s disease, CTE
Excerpted from MedPage Today | By Kay Jackson
Military personnel who reported three or more traumatic brain injuries (TBIs) showed high total tau protein concentrations in plasma, in some cases long after the injuries had occurred, an observational study indicated.
These findings suggest that accumulations of the plasma biomarker, tau, may contribute to chronic neurological symptoms following TBI, Jessica Gill, PhD, RN, of the National Institute of Nursing Research in Bethesda, Md., and colleagues reported online in JAMA Neurology.
“The post-concussive disorder (PCD) symptoms correlating to tau concentrations may be early signs of ongoing neurodegeneration that may benefit from early intervention,” said Gill. “These findings require follow-up to determine temporal relationships related to total tau, TBIs and chronic symptoms.”
Total tau concentration appears to relate to chronic symptoms of PCD that are present for months or years after injury. This suggests there may be a cumulative effect of multiple TBIs on recovery processes, the researchers indicated. Additionally, deposits of hyperphosphorylated tau are well-known features of Alzheimer’s disease and have also been found in the condition known as chronic traumatic encephalopathy or CTE.
The current study linked chronic symptoms of PCD to tau elevations independent of post-traumatic stress disorder (PTSD) and depressive symptoms, said Gill. This sheds new light on previous studies linking the number of TBIs to the severity of post-traumatic stress disorder (PTSD) as well as the onset of depression following TBI.
“Ultimately,” said Gill, “studies that provide a direct mechanistic relationship between TBIs and tau aggregation could support the use of therapeutics such as direct delivery of proteasomes for reducing tau aggregates. This would be invaluable considering the dearth of treatments for TBIs and chronic PCD symptoms.”
Military personnel who sustain one or more TBIs — the signature injury in military personnel deployed for combat operations in Iraq and Afghanistan — develop chronic neurological and psychological symptoms that can significantly impact their health and well-being, noted Gill. Previous studies have shown that experiencing three or more TBIs results in a five-fold increased risk of cognitive impairments and a three-fold increased risk of memory problems, even in young individuals.
“Our findings are consistent with reports for repetitive head injury in athletes linked to progressive tauopathy, axonal injury and PCD symptoms,” noted Gill.
From September 2012 to August 2014, the observational assessment looked at U.S. military personnel at the Madigan Army Medical Center in Tacoma, Wash., who had been deployed within the previous 18 months. Seventy participants with self-reported
TBI on the Warrior Administered Retrospective Casualty Assessment Tool (WARCAT) and 28 control participants with no TBI exposure were included.
Results showed that concentrations of plasma tau were significantly elevated in the 70 participants with self-reported TBI when compared with the 28 controls (mean 1.13 pg/mL, SD 0.78, versus 0.63 pg/mL, SD 0.48; P=0.03).
Within the self-reported TBI cases, plasma total tau concentrations were significantly associated with having a medical record of TBI compared with self-reported TBI only (mean 1.57 pg/mL, SD 0.92, versus 0.85 pg/mL, SD 0.52; P=0.02) as well as reporting the occurrence of three or more TBIs during deployment compared with fewer than three (mean 1.52 pg/mL, SD 0.82, versus 082 pg/mL, SD 0.60; P=0.008).
The severity of total post concussive symptoms correlated with total tau concentrations in the self-reported TBI group (r=0.37, P=0.003), the investigators reported.
In an accompanying editorial, Elaine R. Peskind, MD, of the VA Puget Sound Health Care System in Seattle, cautioned that “whether plasma tau is a useful marker of brain tau pathology in mild TBI remains to be seen.”
According to Peskind, the meaning of plasma tau will depend on:
Correlating plasma and CSF tau
Longitudinal studies of clinical outcomes in service members, veterans and athletes with repetitive mild TBI
Autopsy studies of persons with plasma tau measurements in life
In the meantime, active investigation into the measurement of central nervous system-derived exosomes may provide a more direct measure of brain tau pathology in mild TBI, Peskind concluded.