Glucocerebrosidase mutations confer a greater risk of dementia during Parkinson's disease course

Mov Disord. 2012 Mar;27(3):393-9. doi: 10.1002/mds.24045. Epub 2011 Dec 15.


Mutations in the glucocerebrosidase gene are associated with Parkinson's disease and Lewy body dementia. However, whether these alterations have any effect on the clinical course of Parkinson's disease is not clear. The glucocerebrosidase coding region was fully sequenced in 225 Parkinson's disease patients, 17 pathologically confirmed Lewy body dementia patients, and 186 controls from Spain. Twenty-two Parkinson's disease patients (9.8%) and 2 Lewy body dementia patients (11.8%) carried mutations in the glucocerebrosidase gene, compared with only 1 control (0.5%); P = .016 and P = .021 for Parkinson's disease and Lewy body dementia, respectively. The N370S and the L444P mutations represented 50% of the alterations. Two novel variants, L144V and S488T, and 7 previously described alterations were also found. Alterations in glucocerebrosidase were associated with a significant risk of dementia during the clinical course of Parkinson's disease (age at onset, years of evolution, and sex-adjusted odds ratio, 5.8; P = .001). Mutation carriers did not show worse motor symptoms, had good response to L-dopa, and tended to present the intermediate parkinsonian phenotype. Our findings suggest that mutations in the glucocerebrosidase gene not only increase the risk of both Parkinson's disease and Lewy body dementia but also strongly influence the course of Parkinson's disease with respect to the appearance of dementia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Chi-Square Distribution
  • DNA Mutational Analysis
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Glucosylceramidase / genetics*
  • Humans
  • Lewy Body Disease / complications
  • Lewy Body Disease / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neuropsychological Tests
  • Parkinsonian Disorders / complications
  • Parkinsonian Disorders / genetics*
  • Risk Factors


  • Glucosylceramidase