The SAMP, Senescence-Accelerated Mouse strains show senescence acceleration and age-associated pathological phenotypes similar to geriatric disorders seen in humans. Among these strains, SAMP8 mice show age-associated deficits in learning and memory. Histopathological studies revealed various neurodegenerative changes in the brain, including age-associated appearance of spongiform degeneration in the brain stem and of PAS-positive granular structures in the hippocampus. The blood-brain barrier (BBB) function of SAMP8 mice was also impaired with advancing age. The compromised BBB function in the olfactory bulb, the hippocampus and the pons of SAMP8 mice coincided with and might have been the cause of some morphological changes. Age-associated degeneration of receptor cells and ganglion neurons in the retina and cochlea also occurred in the SAM mice. Oxidative stress partly caused by mitochondrial dysfunction was detected and may be a cause of the neuronal cell degeneration. The SAM strains are useful tool in the attempt to understand the mechanisms of age-dependent neurodegeneration and to develop clinical interventions.