A novel presenilin1 mutation (Q223R) associated with early onset Alzheimer's disease, dysarthria and spastic paraparesis and decreased Abeta levels in CSF

Eur J Neurol. 2010 Apr;17(4):631-3. doi: 10.1111/j.1468-1331.2009.02810.x. Epub 2009 Nov 12.

Abstract

Background and purpose: A novel presenilin1 (PSEN1) mutation associated with dementia and spastic paraplegia in a family with five affected individuals is described. The index patient was a 35-year-old man presenting with cognitive decline, behavioural symptoms, dysarthria, and gait disorder due to spasticity.

Methods and results: Genetic analysis revealed a missense mutation Gln223Arg in exon 7. Initial CSF analysis revealed drastically decreased Abeta42 level despite marginally decreased FDG metabolism.

Conclusion: Cerebrospinal fluid biomarker analysis might point towards genetic analysis of PSEN1 in patients with positive family history and age of onset below 60 years.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Age of Onset
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / pathology
  • Dysarthria / cerebrospinal fluid
  • Dysarthria / genetics*
  • Dysarthria / pathology
  • Family
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation, Missense*
  • Paraparesis, Spastic / cerebrospinal fluid
  • Paraparesis, Spastic / genetics*
  • Paraparesis, Spastic / pathology
  • Pedigree
  • Positron-Emission Tomography
  • Presenilin-1 / genetics*

Substances

  • Amyloid beta-Peptides
  • Presenilin-1
  • Fluorodeoxyglucose F18