Promotes Tonic-Clonic Seizures, an Effect Modified by Familial Alzheimer's Disease Mutations.

Seizures are emerging as a common symptom in Alzheimer's disease (AD) patients, often attributed to high levels of amyloid β (Aβ). However, the extent that AD disease risk factors modulate seizure activity in aging and AD-relevant contexts is unclear. is the greatest genetic risk factor for AD and has been linked to seizures independent of AD and Aβ. The goal of the present study was to evaluate the role of genotype in modulating seizures in the absence and presence of high Aβ levels . To achieve this goal, we utilized EFAD mice, which express human or in the absence (EFAD-) or presence (EFAD+) of familial AD mutations that result in Aβ overproduction. When quantified during cage change day, we found that unlike , is associated with tonic-clonic seizures. Interestingly, there were lower tonic-clonic seizures in E4FAD+ mice compared to E4FAD- mice. Restraint handing and auditory stimuli failed to recapitulate the tonic-clonic phenotype in EFAD mice that express . However, after chemical-induction with pentylenetetrazole, there was a higher incidence of tonic-clonic seizures with compared to . Interestingly, the distribution of seizures to the tonic-clonic phenotype was higher with FAD mutations. These data support that is associated with higher tonic-clonic seizures , and that FAD mutations impact tonic-clonic seizures in a paradigm dependent manner.