We developed a novel inbred strain of mouse with age-related brain atrophy and it was named “Senescence Accelerated Mouse (SAM)-P/10.” Macroscopic morphometry indicated that the brains of SAM-P/10 showed age-dependent involutional changes mainly in the frontal portion of the cerebrum. The brain weight decreased by 8.6% throughout the lifespan. There were no obvious defects in postnatal development. Semi-macroscopic morphometry revealed a prominent atrophy in the neocortex, olfactory cortex and amygdala. Microscopic morphometry showed that the neocortical neurons were lost with aging, with mostly the large neurons being affected which were lost by 35.6% throughout the life-span. Somata of the neocortical neurons shrank with advancing age. In a control SAM-R/1 strain with only a slight macroscopic involutional change in the brain without weight loss, neither loss of the neocortical large neurons nor shrinkage of the neocortical neurons was evident with aging. Learning and memory skills were evaluated using the one-trial passive avoidance task and conditional avoidance task. Young SAM-P/10 mice performed well in both tasks but older SAM-P/10 showed a poorer performance in both tasks, and this was even poorer than the performance of very old SAM-R/1 mice. Thus, SAM-P/10 can serve as a spontaneous animal model of brain atrophy for a variety of studies of aging of the brain. A better understanding of neurodegenerative diseases with dementia should be forthcoming.