Here, we found that HMGB1 and p-tau (Ser404) increased simultaneously during the period when spatial memory impairment occurred, suggesting that the overexpression of p-tau may be mainly responsible for an earlier onset of spatial cognitive dysfunction in patients with TBI rather than in elderly patients with AD through the promotion HMGB1 levels in spatial memory-related brain regions. This evidence concerns the gene HMGB1 and Alzheimer disease.