BACKGROUND: The close relationship between epileptic seizure and Alzheimer's 
disease (AD) has been demonstrated in the past decade. Valproic acid, a 
traditional first-line antiepileptic drug, exerted protective effects in 
transgenic models of AD. It remains uncertain whether new antiepileptic drugs 
could reverse neuropathology and behavioral deficits in AD transgenic mice.
AIMS: APPswe/PS1dE9 transgenic mice were used in this study, which over express 
the Swedish mutation of amyloid precursor protein together with presenilin 1 
deleted in exon 9. 7-month-old APPswe/PS1dE9 transgenic mice were treated daily 
with 20 mg/kg topiramate (TPM) and 50 mg/kg levetiracetam (LEV) for 30 days by 
intraperitoneal injection to explore the effects of TPM and LEV on the 
neuropathology and behavioral deficits.
RESULTS: The results indicated that TPM and LEV alleviated behavioral deficits 
and reduced amyloid plaques in APPswe/PS1dE9 transgenic mice. TPM and LEV 
increased Aβ clearance and up-regulated Aβ transport and autophagic degradation. 
TPM and LEV inhibited Aβ generation and suppressed γ-secretase activity. TPM and 
LEV inhibited GSK-3β activation and increased the activation of AMPK/Akt 
activation. Further, TPM and LEV inhibited histone deacetylase activity in vivo.
CONCLUSIONS: Therefore, TPM and LEV might have the potential to treat AD 
effectively in patient care.