After 13 weeks of treatment, all groups were trained in the water maze exercise to see how quickly they could learn to exit the water via a hidden platform. Doing so requires the use of spatial cues, such as patterned posters or photos, positioned all around the water tank. The Alzheimer's model mice that were fed the control diet predictably showed significant losses in learning and memory and reduced performance.

"Strikingly, the Alzheimer's mice treated with rapamycin displayed improved performance on the maze, even reaching levels that were indistinguishable from their normal littermates," Dr. Galvan said. "Levels of amyloid-beta-42 were also reduced in these mice after treatment, and we are seeing preserved numbers of synaptic elements in the brain areas of Alzheimer's disease mice that are ravaged by the disease process."

Intriguingly, differences in resistance to swimming in the middle of the pool (a measure of anxiety) and in floating (a measure of hopelessness) were not observed among groups. "This suggests that improved performance in rapamycin-treated, Alzheimer's-susceptible mice is a result of effects on purely cognitive processes but is not due to effects related to non-cognitive components of behavior, such as helplessness and anxiety," Dr. Galvan said.

Changing a toxic process

"The fact that we are seeing identical results in two vastly different mouse models of Alzheimer's disease," Dr. Galvan added, in reference to the recent study by Caccamo et al, "provides robust evidence that rapamycin treatment is effective and is acting by changing a basic pathogenic process of Alzheimer's that is common to both mouse models. This suggests that it may be an effective treatment for Alzheimer's in humans, who also have very diverse genetic makeup and life histories."

Source: University of Texas Health Science Center at San Antonio