Repetitive mild traumatic brain injury causes neuronal damage in the APP/PS1 mouse model of Alzheimer's disease without an enduring impact on amyloid pathology, sleep, or epileptiform activity

Yue, J.; Carriquiriborde, V.; Cheng, W. H.; Yildirim, T.; Fan, J.; Tok, S.; Kelly, M.; Wellington, C.; Kent, B.

doi:10.1101/2025.06.06.658157

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bioRxiv · 10.1101/2025.06.06.658157

Repetitive mild traumatic brain injury causes neuronal damage in the APP/PS1 mouse model of Alzheimer's disease without an enduring impact on amyloid pathology, sleep, or epileptiform activity

Yue, J.·Carriquiriborde, V.·Cheng, W. H.·Yildirim, T.·Fan, J.·Tok, S.·Kelly, M.·Wellington, C.·Kent, B.

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Abstract

Traumatic Brain Injury (TBI) is a known risk factor for Alzheimers disease and related neurodegenerative diseases. Sleep disturbances and epileptiform abnormalities can appear after TBI and may contribute to the development of neuropathology. In this study, we characterized sleep, epileptiform activity, and neuropathology after repetitive mild traumatic brain injury (rmTBI) in a mouse model of Alzheimers disease. We used the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) to deliver rmTBI or sham (control) treatment to 6-month-old APP/PS1 mice (N=19). One month post-injury, we implanted electroencephalogram (EEG) and electromyographic (EMG) electrodes, recorded for 72 hours, and then collected brain tissue and blood plasma. Our assessment of sleep architecture showed that time spent in vigilance state was not affected by the rmTBI one month post-injury; however, power spectra analysis showed a shift towards higher frequencies in the rmTBI group during non-rapid eye movement (NREM) sleep. Epileptiform activity did not differ between sham and rmTBI. Compared to sham controls, the rmTBI group showed higher neurofilament light (NF-L), but not glial-fibrillary acidic protein (GFAP) in blood plasma and no change in A{beta} pathology. These results indicate sustained neurological injury in the APP/PS1 mice one month after rmTBI without affecting amyloid deposition in the brain. Our study suggests that rmTBI can induce neural injury without causing enduring sleep disruption, seizures, and exacerbation of amyloidosis in the APP/PS1 mouse model.

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Yue, J., Carriquiriborde, V., Cheng, W. H., Yildirim, T., Fan, J., Tok, S., Kelly, M., Wellington, C., Kent, B.. 2025-06-09. Repetitive mild traumatic brain injury causes neuronal damage in the APP/PS1 mouse model of Alzheimer's disease without an enduring impact on amyloid pathology, sleep, or epileptiform activity. https://doi.org/10.1101/2025.06.06.658157

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