Background and objective: There are many studies that demonstrate correlation between traumatic brain injury (TBI) and Alzheimer's disease (AD). Indeed, several epidemiological examinations have revealed that TBI is an epigenetic risk factor for developing AD. However, it is unclear how TBI contributes to the onset or progression of this late life dementia. To address this question, we studied neuropathological and behavioral consequences of TBI in a triple transgenic AD-model mice (3xTg AD mice) harboring PS1M146V, APPSWE, and tauP301L transgenes. Here, we report that weight drop method TBI in 3xTg AD mice demonstrated amyloid-β (Aβ) depositions and amyloid precursor protein (APP) accumulation at 7 days or 4 weeks after TBI.
Materials and methods: Five to seven-month-old 3xTg AD mice and wild type mice were subjected to TBI (n = 7-10) or sham treatment (n = 7-8). At 7 days and 4 weeks after treatment, we assessed behavioral and cognitive performance, and Aβ depositions and APP accumulation in the hippocampus.
Results: Compared to sham-treatment wild type mice, brain-injured wild type mice exhibited significant impairment in spatial learning as measured using the Morris water maze 7 days after TBI (p = 0.024), however, after 4 weeks, the spatial learning deficit in the brain-injured wild type mice was recovered to the same level in the sham-treatment wild type mice (p = 0.040). In contrast, even after 4 weeks, TBI-treated 3xTg AD mice exhibited significant cognitive deficits in spatial learning (p = 0.064) accompanied by increased Aβ depositions in the hippocampus (p = 0.018). No mice have motor deficits at any time. These results suggested that TBI induced cognitive impairment but no motor deficit in these mice.
Conclusion: These results provide the experimental evidence linking TBI to mechanism of AD by showing that TBI induces brain cognitive impairment accompanied with Aβ depositions.