Overpressure Exposure From .50-Caliber Rifle Training Is Associated With Increased Amyloid Beta Peptides in Serum

Abstract

Background: Overpressure (OP) is an increase in air pressure above normal atmospheric levels. Military personnel are repeatedly exposed to low levels of OP caused by various weapon systems. Repeated OP may increase risk of neurological disease or psychological disorder diagnoses. A means to detect early phase effects that may be relevant to brain trauma remain elusive. Therefore, development of quantitative and objective OP-mediated effects during acute timeframes would vastly augment point-of-care or field-based decisions. This pilot study evaluated the amplitude of traumatic brain injury (TBI)-associated biomarkers in serum as a consequence of repeated OP exposure from .50-caliber rifle use over training multiple days. Objective: To determine the acute temporal profile of TBI-associated serum biomarkers and their relationship with neurocognitive decrements or self-reported symptoms among participants exposed to low-level, repeated OP from weapons used in a training environment. Methods: Study participants were enrolled in .50-caliber sniper rifle training and exposed to mild OP (peak pressure 3.8-4.5 psi, impulse 19.27-42.22 psi-ms per day) for three consecutive days (D1-D3). Defense automated neurobehavioral assessment (DANA) neurocognitive testing, symptom reporting, and blood collection were conducted 2-3 h before (pre-) and again 0.45-3 h after (post-) OP exposure. The TBI-associated serum biomarkers, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neurofilament light (Nf-L), tau, and amyloid beta peptides (Aβ-40 and Aβ-42) were measured using digital ELISAs. Results: Serum GFAP decreased on D1 and D3 but not D2 after OP exposure. Nf-L was suppressed on D3 alone. Aβ-40 was elevated on D2 alone while Aβ-42 was elevated each day after OP exposure. Suppression of GFAP and elevation of Aβ-42 correlated to OP-mediated impulse levels measured on D3. Thangavelu et al. Amyloid Beta Peptides After Overpressure Conclusions: Acute measurement of Aβ-peptides may have utility as biomarkers of subconcussive OP caused by rifle fire. Fluctuation of GFAP, Nf-L, and particularly Aβ peptide levels may have utility as acute, systemic responders of subconcussive OP exposure caused by rifle fire even in the absence of extreme operational deficits or clinically defined concussion.

Mathematical model of mechanobiology of acute and repeated synaptic injury and systemic biomarker kinetics

“…Moreover, our model predicts that the plasma biomarkers remain elevated for months after the initial exposure. Our findings of increased Aß 42 in plasma 3-5 days post-blast exposure compare relatively well to recently reported human plasma Aß 42 and Aß 40 levels 1-, 2-and 3-days post-weapon blast exposure in military sniper training (Thangavelu et al, 2020;Boutté et al, 2021). We are collecting related human blast dose biomarker response data for more quantitative model validation.…”

Blast effects on post-concussive and mental health outcomes: Data from Canadian Armed Forces breachers and snipers

“…Recently, Thangavelu et al measured the amplitude of TBI-associated biomarkers in serum over three days of .50-caliber sniper rifle training, during which Blast effects on post-concussive and mental health outcomes snipers were exposed to blast overpressure (peak pres sure 3.8-4.5 psi, impulse 19.27-42.22 psi-ms per d). 39 Furthermore, each sniper was equipped with a blast gauge sensor mounted on the left shoulder, to obtain the peak overpressure and impulse values associated with each blast event. Results demonstrated the suppres sion of glial fibrillary acidic protein and elevation of an amyloid beta peptide were correlated with overpressuremediated impulse levels measured on the third day of training, suggesting the amplitude of TBI-associated biomarkers in serum can be used as markers of blast overpressure caused by rifl e fire.…”

Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury

“…Service members with blast-induced mTBI have significantly higher rates of physical and mental health problems compared to soldiers with other non-neurological injuries. Awareness of potential consequences of LIB exposures has been raised by studies reporting the capacity of various types of weaponry to generate injurious blast overpressures during military and law enforcement trainings (13)(14)(15). LIB-induced mTBI injuries in Service members and law enforcement personnel have been associated with chronic subclinical effects (16).…”