title: Presenilin-1 mutation Alzheimer's disease: a genetic epilepsy syndrome?
abstract: Mutations in the presenilin-1 gene (PSEN1) on chromosome 14 are the most common cause of autosomal dominant Alzheimer's disease (AD), with around 180 mutations described to date. PSEN1 AD has a broad clinical phenotype, encompassing not only dementia but a variety of other neurological features which may include epileptic seizures. Around 20% of recorded PSEN1 mutations have been reported to be associated with epileptic seizures, sometimes occurring as an early feature of disease, sometimes late. The epilepsy-associated PSEN1 mutations are spread throughout the PSEN1 gene. This frequency of seizure-associated PSEN1 mutations may be an underestimate, as epileptic seizures may not be recognized as such in the context of a dementing disorder, perhaps being labeled as "confusion" or delirious episodes. A high index of clinical suspicion for epileptic seizures in PSEN1 AD is therefore appropriate. The neuropathological substrates of PSEN1 AD-related seizures remain to be determined, as few such cases have undergone detailed neuropathological examination. Nevertheless, PSEN1 AD should now be recognized, using the new International League Against Epilepsy nomenclature, as a genetic epilepsy syndrome.
authors.affiliation: Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Liverpool, UK. a.larner@thewaltoncentre.nhs.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Larner
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics*; D004827:Epilepsy / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1