Traumatic brain injury accelerates amyloid-β deposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease

Several pathological and epidemiological studies have demonstrated a possible relationship between traumatic brain injury (TBI) and Alzheimer's disease (AD). However, the exact contribution of TBI to AD onset and progression is unclear. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in triple transgenic (3 xTg)-AD model mice. Five- to seven-month-old 3 xTg-AD model mice were subjected to either TBI by the weight-drop method or a sham treatment. In the 3 xTg-AD mice subjected to TBI, the spatial learning was not significantly different 7 days after TBI compared to that of the sham-treated 3xTg-AD mice. However, 28 days after TBI, the 3 xTg-AD mice exhibited significantly lower spatial learning than the sham-treated 3xTg-AD mice. Correspondingly, while a few amyloid-beta (A beta) plaques were observed in both sham-treated and TBI-treated 3 xTg-AD mouse hippocampus 7 days after TBI, the A beta deposition was significantly greater in 3 xTg-AD mice 28 days after TBI. Thus, we demonstrated that TBI induced a significant increase in hippocampal A beta deposition 28 days after TBI compared to that of the control animals, which was associated with worse spatial learning ability in 3 xTg-AD mice. The present study suggests that TBI could be a risk factor for accelerated AD progression, particularly when genetic and hereditary predispositions are involved. (C) 2016 Elsevier Ireland Ltd. All rights reserved.