Tau biomarkers in Special Operations Forces with repeated blast exposure: a cross-sectional study

Abstract

US Special Operations Forces (SOF) personnel endure repeated blasts throughout training and combat. Recent human postmortem, neuroimaging and blood proteomic work suggest that tau pathology is present following repeated blast exposure. This study aimed to determine whether blood tau markers are associated with brain tau paired helical filaments (PHFs) in SOF personnel. Twenty-eight active-duty SOF completed a positron emission tomography-magnetic resonance imaging scan with the PHF-specific radiotracer fluorine-18 MK6240 ([¹⁸F]MK6240) and provided blood samples to measure total tau and phosphorylated tau181 (p-tau181). Whole brain voxel-wise analysis showed that higher total tau in the blood was associated with higher [¹⁸F]MK6240 uptake in the left temporal cortex, parahippocampal gyrus and hippocampus. We performed post hoc analyses to assess whether brain or blood tau measures were associated with memory performance. Higher levels of blood total tau and p-tau181 were associated with a longer response time and lower throughput (i.e. fewer accurate responses per minute) during the Code Substitution-Delayed test, a visual memory task in the Automated Neuropsychological Assessment Metrics (ANAM). This study provides preliminary evidence in active-duty SOF that blood total tau is associated with regional [¹⁸F]MK6240 uptake in the brain and that blood total tau and p-tau181 are associated with memory performance.

Keywords: blood biomarker; neuroimaging; tau.

Graphical Abstract

Figure 1

Relationship between brain PHF tau measured by [¹⁸F]MK6240 PET and blood total tau in active-duty SOF. Blood total tau levels were positively associated with PHF as measured by [¹⁸F]MK6240 SUVR in a region encompassing the left temporal cortex, left parahippocampal gyrus and left hippocampus. Image shows a statistical map of linear regression with total tau and [¹⁸F]MK6240 SUVR, controlling for age [threshold of Z > 2.3, beta = 1.23 × 10⁻², 95% CI (1.22 × 10⁻², 1.23 × 10⁻²), P_cluster < 0.05], overlaid on a 500-micron quantitative multi-echo flash template in MNI space. R = right, SUVR = standardized uptake value ratio, PHF = paired helical filament.