Epidemiological studies have shown brain injury is a risk factor for Alzheimer's disease(AD). Dementia pugilistica observed with ex-boxers after more than ten years was once claimed rich with neurofibrillary tangles but not with senile plaques, however, the recent studies have demonstrated abundent amyloid deposits implying the similarity with AD. The purpose of the study is to examine the hypothesis the repetition of mild mechanical brain injury induces the pathological changes related with AD. Brain mechanical injury was loaded to the rat brain by fluid percussion apparatus. Firstly, the effect of graded single impact was evaluated (1.0-4.3 atm) to find out the minimum magnitude of impact causing neuronal degeneration. The 1.0 atm impact was shown to induce HSP72 without causing MAP2 or neurofilament dislocalization. Then the effect of the repetition of 1.0 atm impact was studied. The behavioral study of the rats loaded with repetitive mild injury showed the suppressed habituation to the new environment. The suppression was more clearly demonstrated when the interval of the impact was shortened and the number of impact was increased, implying the dose-dependent cerebral dysfunction. One week after seven times repetition of 1.0 atm impact, abnormal accumulation of MAP2 and phosphorylated neurofilament H (NFH) was observed in neuronal perikarya around the impact site. The number of MAP2- and phosphorylated NFH- positive neurons was increased and observed in more remote area one month after the impact, implying the self accelerating process. It is suggested that the repetition of the subthreshold mechanical brain injury could trigger microtubule and neurofilament alteration which may eventually lead to neuronal degeneration.