P2‐435: GEPT extract prevents Aβ deposition–induced synaptic loss in APPV717I transgenic mice through improving synaptophysin

Deficits in synaptic communication and plasticity are crucial in the development of Alzheimer's disease (AD). Density of the presynaptic markers, especially the synaptophysin (SYN) is well correlated with disease progression and cognitive decline in AD. Therefore, in addition to reduce the deposition of Abeta by the inhibition of its production and the facilitation of its degradation, synaptic protection is another therapeutic strategy for AD. Thus, aim of this study was to investigate effects of GEPT extract, a combination of several active components extracted from Chinese herbs, on synaptic protection in the brain of APPV717I transgenic mice. Three-month-old APPV717I mice were randomly divided into ten groups (n = 12 per group) and they were intragastrically administrated water or medicines accordingly for 8 or 4 months. Same age and male C57BL/6J mice (n = 12) were given as a vehicle for 8 or 4 months as well. Immunohistochemistry (IHC) and Western blot analysis were used in determining protein expressions in hippocampal CA1 region and ratios of synaptophysin/beta-actin hippocampal tissue homogenate. In this study, IHC and Western blot both showed a significant decrease of synaptophysin expression in CA1 region of 7 and 11 months old APPV717I transgenic mice (APP group) compared to Vehicle group, while the synaptophysin expression of donepezil or GEPT treated APP group were all restored to certain level compared to APP group alone. IHC showed a significant difference in synaptophysin expression between GEPT high dose group and APP group (P <0.05) after 4 months treatment, and a significant difference in synaptophysin expression of three GEPT groups respectively compared to the APP group alone (P <0.01 to P <0.05) after 8 months treatment. Western blot showed that ratios of synaptophysin protein/beta-actin in APP group alone significantly decreased, APP group treated by donepezil or GEPT were all restored to certain level, but there were no significant differences between APP groups treated by donepezil and GEPT. GEPT extract has significant effectiveness in preventing Aβ deposition induced synaptic loss in APPV717I transgenic mice through improving synaptophysin with a dose-dependent effect.