A novel PSEN1 mutation in a patient with sporadic early-onset Alzheimer's disease and prominent cerebellar ataxia

J Alzheimers Dis. 2014;41(3):709-14. doi: 10.3233/JAD-140081.

Abstract

PSEN1 gene mutations represent the first cause of familiar early-onset Alzheimer's disease (EOAD). More than 190 mutations in PSEN1 have been reported to date. The clinical phenotype is mainly characterized by cognitive decline but movement disorders have been rarely described. We report a novel PSEN1 mutation (p.Thr147Pro) responsible for a sporadic early-onset dementia with prominent cerebellar symptoms, resembling a spinocerebellar syndrome. Neuroradiological and cerebrospinal fluid biomarkers examinations were performed on the patient, showing typical findings of EOAD and suggesting the pathogenicity of the novel mutation. Our study widens the number of unusual phenotypes related to PSEN1 mutations.

Keywords: Ataxia; dominantly-inherited spinocerebellar ataxias; early onset Alzheimer's disease; human PSEN1 protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / complications
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics*
  • Cerebellar Ataxia / complications
  • Cerebellar Ataxia / diagnosis
  • Cerebellar Ataxia / drug therapy
  • Cerebellar Ataxia / genetics*
  • Cholinesterase Inhibitors / therapeutic use
  • DNA Mutational Analysis
  • Donepezil
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Indans / therapeutic use
  • Magnetic Resonance Imaging
  • Male
  • Mutation / genetics*
  • Piperidines / therapeutic use
  • Positron-Emission Tomography
  • Presenilin-1 / genetics*
  • Young Adult

Substances

  • Cholinesterase Inhibitors
  • Indans
  • PSEN1 protein, human
  • Piperidines
  • Presenilin-1
  • Fluorodeoxyglucose F18
  • Donepezil