title: Lrrk2 and Lewy body disease.
abstract: OBJECTIVE
  The Lrrk2 kinase domain G2019S substitution is the most common genetic basis of familial and sporadic parkinsonism. Patients harboring the G2019S substitution usually present with clinical Parkinson's disease.
  
  
  METHODS
  Herein, we report that the most common neuropathology of G2019S-associated Parkinson's disease is Lewy body disease.
  
  
  RESULTS
  Lrrk2 G2019S was observed in approximately 2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The mutation was also found in one control subject and one Alzheimer's disease patient, reflecting reduced penetrance.
  
  
  CONCLUSIONS
  Therapeutic strategies targeted at modulating Lrrk2 kinase activity may be important to treat patients with genetically defined familial or typical sporadic Parkinson's disease.
authors.affiliation: Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL 32224, USA.
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: Mathias
authors.initials: M
authors.lastname: Toft
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Whittle
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Spiridon
authors.initials: S
authors.lastname: Papapetropoulos
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.forename: Irene
authors.initials: I
authors.lastname: Litvan
authors.forename: Mark F
authors.initials: MF
authors.lastname: Gordon
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D020961:Lewy Body Disease / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics
chemical_list: D011506:Proteins; C475853:serin-rich spermatogenic protein 1, rat; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine