Knowledge Bank

Traumatic brain injury (TBI) impacts at least 1.5 million people every year and is an environmental risk factor for Alzheimer's Disease (AD). Notably, specific genetic risk loci have been identified to greatly increase the risk of developing Late Onset AD (LOAD). Two of these genetic risk factors include the Apolipoprotein E4 (Apoe4) allele and the Triggering Receptor Expressed on Myeloid Cells 2 (Trem2) R47H variant. These factors have been shown to work synergistically with TBI to worsen functional outcome and exacerbate neuroinflammatory processes. It is shown that incidence of both TBI and LOAD contribute to chronic sleep disruptions (1, 2). The aim of this study is to investigate how these genetic risk factors interact with TBI to influence sleep-wake regulation. To investigate this interaction, we employed lateral fluid percussion injury (LFPI) on mice containing either the APOE3 allele as a genetic control or the APOE4 allele and TREM2R47H variant. Sleep was monitored up to 14 days post injury (DPI) using implanted electroencephalogram/electromyograph (EEG/EMG) telemetry sensors and subsequently analyzed to examine differences in sleep-wake stages as well as in sleep- wake bouts. We hypothesized that mice with both TBI and the A4/Trem2R47H genotype would have increased dysfunction in sleep expression, sleep quality, and sleep consolidation compared to A3 controls. We found that the A4/Trem2R47H mice spent less time sleeping in REM and had a lower number of REM sleep bouts, which indicates that genotype impacts sleep independent of the presence of TBI. While previous studies signal that TBI has little to no effect on REM sleep, our data points out that may not necessarily be the case. There were little to no significant differences in time spent in NREM sleep or wake, or number or length of NREM or wake bouts.