We hypothesized that epileptogenesis and Alzheimer’s Disease are part of a positive feedback loop and that the mTOR pathway may be a treatable modifier of AD progression. 

Patients with AD have an elevated risk of developing seizures, particularly in patients with early onset familial Alzheimer’s Disease (FAD) and severe AD. Seizures may worsen AD pathology and hasten the progression of the disease, making their investigation in this population a worthwhile target for intervention.

Post-mortem temporal cortex samples from 13 control subjects and 34 AD patients (14 with a known clinical seizure history, 20 without known seizure episodes) were obtained from the Institute on Aging – Center for Neurodegenerative Disease and Research. Pathological autopsy reports were used to extract disease duration, ventricular enlargement severity, and brain weight at death. Human temporal cortex samples were homogenized and whole cell and membrane fractions were obtained. Soluble Aβ₄₂ concentration was measured using an anti-human Aβ₄₂ ELISA kit. Western blots were performed with the whole cell and membrane fractions to measure tau hyperphosphorylation and phosphorylated S6 expression.