Abstracts

Summary: For a long time, patients with Alzheimer's disease (AD) have been known to have myoclonic seizures. Recently it was shown that the risk of unprovoked partial or generalized seizures is increased up to 86-fold in patients with an early onset of AD. Moreover, it was hypothesized that daily cognitive fluctuations in AD could relate to the occurrence of undiagnosed complex partial seizures. Recently, many different mouse strains that overexpress mutated form of amyloid precursor protein (APP), show spontaneous seizures and have interictal epileptiform discharges. These studies raise questions: what triggers multiple seizure types or hyperexcitability in AD? Recent data suggest that amyloid precursor protein (APP) cleavage products may be involved because they can modulate several ion channels. Furthermore, enzymes contributing to APP processing may use Na-channel subunits as substrates, and consequently, affect Na-channel trafficking and composition in cell membranes. In this IW, we first discuss the ways different mutations in mice and patients with AD pathology might cause epilepsy in AD. Then we ask if the effects of amyloidogenic APP processing on neuronal excitability is sufficient to explain seizure generation. We also consider the role of Na-channelopathy in seizure generation in mice and patients with AD. Finally, we address the question whether abnormal network re-organization could be the critical factor in seizure generation.