Recent studies suggest that Cerebrolysin improves behavioral performance by affecting synaptic transmission in the hippocampus. The main objective of this study was to determine if Cerebrolysin administration ameliorates the neurodegenerative and performance deficits in aged apolipoprotein E (apoE)-deficient mice. ApoE-deficient mice treated with Cerebrolysin showed a significant improved performance in the Morris water maze, compared to saline-treated apoE-deficient mice. Although the improved performance in the Cerebrolysin-treated apoE-deficient mice was associated with restoration of the neuronal structure, the poor learning ability of saline-treated apoE-deficient mice was related to the a disrupted synaptodendritic structure. This study supports the contention that Cerebrolysin might have a neurotrophic effect in vivo.