Objective:To investigate the changes of the myelinated nerve fibers in the dent-ate gyrus(DG)of the 16-month-old male APP/PS1 transgenetic model mice using the unbiased s-tereological methods in order to further understand the morphological changes in the hippoca-mpus of the Alzheimer’s disease. Methods:The spatial learning and memory abilities of the 16month-old male APP/PS1 model and wild-type mice were investigated using the Morris Water Maze test. The total length of the myelinated fibers

the total volumes of the myelinated fibers

the axons of the myelinated fibers and the myelin sheaths of the myelinated fibers

the inner diameter and outer diameter of the myelinated fibers in the DG of the mice in two groups were investigated by the transmission electron microscope and the unbiased stereological methods. Results:Morris Water Maze results showed that the escape latency of the model mice was signi-ficantly higher than that of the wild-type mice(group effect:F=9.952

P=0.008;time effect:F=3.082

P=0.023;time group interaction:F=0.312

P=0.873). The target zone frequency in the probe trial task of the model mice was significantly decreased compared with that of the wild-type(F=2.961

P=0.011)

so was the percentage of time in target quadrant zone(F=0.090

P=0.002). The hippocampal volume and the dentate gyrus volume were not significantly different between the model mice and the wild-type mice. However

the myelin sheaths of the myelinated fibers in the DG of both group mice existed degenerative changes.Moreover

the stereological results showed that the total length of the myelinated fibers with the diameter range from 0.7 to 1.2μm in the DG of the model mice was significantly decreased when compared with that of wild-type mice(P=0.022). Conclusion:The spatial learning and memory abilities of the 16-month-old male APP/PS1 model mice were decreased significantly. The significant loss of myelinated fibers with the diameter range from 0.7 to1.2 μm in the DG of the APP/PS1 model mice might be one of the structural bases for the memory and learning deficits of the old APP/PS1 model mice.