Amyloid β-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy

Alzheimer's disease is associated with an increased risk of unprovoked seizures. However, the underlying mechanisms of seizure induction remain elusive. Here, we performed video-EEG recordings in mice carrying mutant human APPswe and PS1dE9 genes (APdE9 mice) and their wild-type littermates to determine the prevalence of unprovoked seizures. In two recording episodes at the onset of amyloid beta (Abeta) pathogenesis (3 and 4.5 months of age), at least one unprovoked seizure was detected in 65% of APdE9 mice, of which 46% had multiple seizures and 38% had a generalized seizure. None of the wild-type mice had seizures. In a subset of APdE9 mice, seizure phenotype was associated with a loss of calbindin-D28k…

• AA
  Alzheimer's Association
• AR
  Alzheimer's Research Trust
• EC
  European Commission

  Award: 201159
• IN
  Institut National de la Santé et de la Recherche Médicale
• AO
  Academy of Finland
• SK
  Suomen Kulttuurirahasto
• MR
  Medical Research Council