Age-dependent cerebral atrophy and cognitive dysfunction in SAMP10 mice.

Findings obtained from a series of studies to characterize age-dependent changes in brain morphology and behavior of inbred SAMP10 mice are reviewed. Following apparently normal development, SAMP10 mice developed brain atrophy with advancing age. The neocortex was diffusely atrophic in aged SAMP10 mice, with the frontal cortex being most affected. The entorhinal cortex, amygdala, and nucleus accumbens were also atrophic. Other subcortical structures were mildly atrophic, but the hippocampus was not atrophic. Mild to moderate hypertrophic astrocytosis was seen in the atrophied regions. Alzheimer's type pathology was not seen. The cortical atrophy was due to both loss and shrinkage of neurons. Brain atrophy was not remarkable in normal aging control SAMR10 mice. In accordance with above morphological changes, SAMP10 mice developed cognitive impairments with advancing age that were demonstrated by poor performance in passive avoidance and conditional avoidance tasks. All of these features of SAMP10 mice were inherited. SAMP10, therefore, is a unique model of age-dependent, inherited cerebral atrophy with cognitive dysfunction.