Moderate blast exposure alters gene expression and levels of amyloid precursor protein

Abstract

Objective: To explore gene expression after moderate blast exposure (vs baseline) and proteomic changes after moderate- (vs low-) blast exposure.

Methods: Military personnel (N = 69) donated blood for quantification of protein level, and peak pressure exposures were detected by helmet sensors before and during a blast training program (10 days total). On day 7, some participants (n = 29) sustained a moderate blast (mean peak pressure = 7.9 psi) and were matched to participants with no/low-blast exposure during the training (n = 40). PAXgene tubes were collected from one training site at baseline and day 10; RNA-sequencing day 10 expression was compared with each participant's own baseline samples to identify genes and pathways differentially expressed in moderate blast-exposed participants. Changes in amyloid precursor protein (APP) from baseline to the day of blast and following 2 days were evaluated. Symptoms were assessed using a self-reported form.

Results: We identified 1,803 differentially expressed genes after moderate blast exposure; the most altered network was APP. Significantly reduced levels of peripheral APP were detected the day after the moderate blast exposure and the following day. Protein concentrations correlated with the magnitude of the moderate blast exposure on days 8 and 9. APP concentrations returned to baseline levels 3 days following the blast, likely due to increases in the genetic expression of APP. Onset of concentration problems and headaches occurred after moderate blast.

Conclusions: Moderate blast exposure results in a signature biological profile that includes acute APP reductions, followed by genetic expression increases and normalization of APP levels; these changes likely influence neuronal recovery.

Figure 1. Ingenuity pathway analysis results depicting APP as the network with the highest score

The network was generated using IPA (QIAGEN INC., qiagenbioinformatics.com/products/ingenuity-pathway-analysis). APP = amyloid precursor protein.

Figure 2. Average APP concentrations in the moderate (n = 29) and no/low (n = 40) blast-exposed groups during the 10-day period

Differences in APP concentrations over time (F_1,68 = 12.39, p < 0.01) were observed, with the moderate blast group exhibiting reductions on days 8* and 9* (p's < 0.05). APP = amyloid precursor protein.

Figure 3. Changes in APP from baseline to days 7, 8, and 9 in the moderate (n = 29) and no/low (n = 40) blast-exposed groups

There was no correlation between mean changes in APP from baseline to peak pressure measurements on day 7 (p > 0.10) (A). The mean changes in APP from baseline correlated with peak pressure measurements (in psi) on day 8 (r = 0.62, p < 0.01) (B) and day 9 (r = 0.59, p < 0.01) (C). APP = amyloid precursor protein.