Seizures in Alzheimer's disease

Neuroscience. 2015 Feb 12;286:251-63. doi: 10.1016/j.neuroscience.2014.11.051. Epub 2014 Dec 4.


Alzheimer's disease (AD) increases the risk for late-onset seizures and neuronal network abnormalities. An elevated co-occurrence of AD and seizures has been established in the more prevalent sporadic form of AD. Recent evidence suggests that nonconvulsive network abnormalities, including seizures and other electroencephalographic abnormalities, may be more commonly found in patients than previously thought. Patients with familial AD are at an even greater risk for seizures, which have been found in patients with mutations in PSEN1, PSEN2, or APP, as well as with APP duplication. This review also provides an overview of seizure and electroencephalography studies in AD mouse models. The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability. Nonconvulsive epileptiform activity, such as seizures or network abnormalities that are shorter in duration but may occur with higher frequency, may contribute to cognitive impairments characteristic of AD, such as amnestic wandering. Finally, the review discusses recent studies using antiepileptic drugs to rescue cognitive deficits in AD mouse models and human patients. Understanding the mechanistic link between epileptiform activity and AD is a research area of growing interest. Further understanding of the connection between neuronal hyperexcitability and Alzheimer's as well as the potential role of epileptiform activity in the progression of AD will be beneficial for improving treatment strategies.

Keywords: Alzheimer’s disease; amyloid precursor protein; amyloid β; antiepileptic therapy; mouse models; seizures.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain / physiopathology*
  • Disease Models, Animal
  • Electroencephalography
  • Humans
  • Mice
  • Nerve Net / physiopathology
  • Neurons / pathology
  • Risk Factors
  • Seizures / drug therapy
  • Seizures / etiology*
  • Seizures / genetics


  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor