The Role of Glutamate in the Pathogenesis of Acquired Epilepsy in Alzheimer’s Disease

Alzheimer’s disease (AD) patient has up to 10-fold higher risk of developing epilepsy compared to healthy controls. However, the mechanism that links AD pathologies to epileptic seizures is not elucidated. Disruption to glutamate-glutamine cycle in the brain caused by AD has the potential to enhance this risk. I found that the amount of key components in the glutamate-glutamine cycle, such as GLT-1, were altered in the seizure-prone mouse model of AD. Also, pharmacologically enhancing GLT-1 level reduced the seizure severity in the same model. Thus, disruption to glutamate-glutamine cycle can be one of the links between AD and epilepsy.