The influence of GAPT extraction on synapse loss of APPswe/PS1dE9 transgenic mice via adjusting Bcl-2/Bax balance.

Introduction: The degeneration of memory-focused synapses play important roles in Alzheimer's disease (AD) pathogenesis, while it is not well known how β amyloid interferes neuron apoptosis and how a herbal combination GAPT influence synapse loss and neuronal apoptosis pathways of APP/PS1 transgenic mice.

Methods: Three-month and six-month APPswe/PS1dE9 transgenic mice were used. Spatial and memory ability were measured by Morris Water Maze, Neuron and synapse number were assessed by electron microscope; Aβ, Bcl-2/Bax were determined by immunohistochemistry and western blot.

Results: APP/PS1 mice not only had increased Aβ accumulation, impaired memory performance, less synapse number, and much more necrosed neurons, but also had significant reduction in the Bcl-2/Bax ratio. However, GAPT and donepezil showed improved memory performance, less Aβ accumulation, increased neuron and synapse number, as well as restored balance of Bcl-2/Bax.

Discussion: GAPT may improve cognitive functions via both reducing Aβ deposition and restoring Bcl-2/Bax balance of neuron.