Spatial Training Attenuates Long-Term Alzheimer's Disease-Related Pathogenic Processes in APP/PS1 Mice

Background: Alzheimer's disease (AD), with cognitive impairment as the main clinical manifestation, is a progressive neurodegenerative disease. The assembly of amyloid-β (Aβ) as senile plaques is one of the most well-known histopathological alterations in AD. Several studies reported that cognitive training reduced Aβ deposition and delayed memory loss. However, the long-term benefits of spatial training and the underlying neurobiological mechanisms have not yet been elucidated.

Objective: To explore the long-term effects of spatial training on AD-related pathogenic processes in APP/PS1 mice.

Methods: We used Morris water maze (MWM), Open Field, Barnes Maze, western blotting, qPCR, and immunofluorescence.

Results: One-month MWM training in APP/PS1 mice at 2.5 months of age could attenuate Aβ deposition and decrease the expression of β-secretase (BACE1) and amyloid-β protein precursor (AβPP) with long-term effects. Simultaneously, regular spatial training increased the expression of synapse-related proteins in the hippocampus. Moreover, MWM training increased adult hippocampal neurogenesis in AD model mice. Nonetheless, cognitive deficits in APP/PS1 transgenic mice at 7 months of age were not attenuated by MWM training at an early stage.

Conclusion: Our study demonstrates that MWM training alleviates amyloid plaque burden and adult hippocampal neurogenesis deficits with long-term effects in AD model mice.