A relationship between Alzheimer’s disease and herpes simplex virus infection has been pointed out. We established a model of Alzheimer’s disease with a latent herpesvirus infection using a mouse model of Alzheimer’s disease (PS2Tg2576) and examined the changes in amyloid β (Aβ) in the brain. We crossbred female PS2 mice with male Tg2576 hemi mice and chose PS2Tg2576 mice. After priming 5-week-old male mice with anti-pseudorabies virus swine serum, we challenged the mouse with 100 LD₅₀ of YS-81, a wild-type strain of pseudorabies virus. The viral DNA was detected in nasal swabs by a reactivation test and in the trigeminal ganglia. At two months after infection, the Aβ40 and Aβ42 levels in the brains of the mice of the latently infected group were increased; the increase was greater than that observed in the noninfected group. Latent pseudorabies virus infection was established in PS2Tg2576 mice and the level of Aβ increased with the reactivation of the latent virus.