The effect of increasing amounts of amyloid beta-protein (Abeta) on the number of neurons in the striatum was investigated in APPswe/PS1DeltaE9 transgenic mice. This mouse model of Alzheimer's disease-like amyloidosis displays an increased expression of Abeta in the brain with age. On the basis of reports of disruptions in the anatomy of this part of the brain and the neurotoxic effects of amyloid, it was hypothesized that there would be an age-related decrease in the number of neurons in this part of the brain as a consequence of the age-related increase of Abeta. Estimates of the number of principal neurons of the striatum and the volume of the striatum were made with modern design based stereological techniques in 6- and 12-month-old groups of transgenic and wild type mice. In the 6-month-old groups there was no significant difference in the number of neurons in the striatum. There was a significantly smaller number of neurons in the striatum of the 12-month-old transgenic mice compared to 12-month-old wild type and 6-month-old transgenic mice. There were no significant differences in the volumes of the striatum in any of the four groups of mice studied. The age-related decrease in striatal neuron number is inversely related to an increase in the production of Abeta and suggests a causal relationship between the two.