Lrrk2 G2019S substitution in frontotemporal lobar degeneration with ubiquitin-immunoreactive neuronal inclusions

Acta Neuropathol. 2007 May;113(5):601-6. doi: 10.1007/s00401-006-0178-1. Epub 2006 Dec 7.

Abstract

Leucine-rich repeat kinase 2 (LRRK2) mutation carriers can develop clinical symptoms other than typical parkinsonism such as dementia, amyotrophy or dystonia. To determine if LRRK2 mutations might be involved in frontotemporal dementia (FTD), 5 individuals with multiplex familial FTD kindreds and 41 pathologically confirmed cases of FTD, including 23 with a family history of dementia, were screened for genetic variations in the LRRK2 gene. We identified a LRRK2 mutation leading to the G2019S amino acid substitution in a 79-year-old woman with frontotemporal lobar degeneration with ubiquitinated neuronal intranuclear inclusions (FTLD-U/NII) and a possible family history of tremor. These findings may be coincidental; however, there is a small nucleus of LRRK2-positive patients displaying atypical features suggesting a role for this protein in other neurodegenerative disorders.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Amino Acid Substitution / genetics*
  • Dementia* / genetics
  • Dementia* / metabolism
  • Dementia* / pathology
  • Female
  • Glycine / genetics
  • Humans
  • Inclusion Bodies / metabolism*
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Neurons / pathology*
  • Protein Serine-Threonine Kinases / genetics*
  • Serine / genetics
  • Ubiquitin / metabolism*

Substances

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