Increased frequency of the LRRK2 G2019S mutation in an elderly Ashkenazi Jewish population is not associated with dementia

Neurosci Lett. 2006 Jul 10;402(1-2):92-6. doi: 10.1016/j.neulet.2006.03.044. Epub 2006 Apr 24.

Abstract

Mutations in leucine-rich repeat kinase 2 gene (LRRK2) have been associated with idiopathic Parkinson's disease (PD), as well as pleomorphic neurodegenerative pathology, including Alzheimer's disease. One specific LRRK2 mutation, G2019S, was reported in 18% of people with PD of Ashkenazi descent, supporting a founder effect in this population. To determine if this mutation is also associated with dementia in the Ashkenazim, we screened 192 elderly Ashkenazi Jewish (AJ) individuals in a longitudinal aging and cognition study, of whom 49 (25.5%) had dementia. Two non-demented individuals harbored the mutation (2/143, 1.4%), but no individuals with dementia. Neither person with the mutation had Parkinson's disease. Therefore, the LRRK2 mutation has a relatively high frequency in the AJ population, is not fully penetrant for parkinsonism in the elderly, and does not appear to be commonly associated with late-onset dementia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged, 80 and over
  • Aging*
  • DNA Mutational Analysis / methods
  • Dementia / genetics*
  • Female
  • Glycine / genetics*
  • Humans
  • Jews / ethnology
  • Jews / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Mutation*
  • Protein Serine-Threonine Kinases / genetics*
  • Residence Characteristics
  • Serine / genetics*

Substances

  • Serine
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Protein Serine-Threonine Kinases
  • Glycine