title: LRRK2 variation and dementia with Lewy bodies.
abstract: The leucine-rich repeat kinase 2 (LRRK2) gene contains several variants that cause Parkinson's disease (PD) and others that modify PD risk. However, little is known about the role of LRRK2 in dementia with Lewy bodies (DLB). Aims of this study were to screen DLB patients for pathogenic LRRK2 variants and to evaluate associations between common LRRK2 variants and risk of DLB.
  
  
  
  417 clinical DLB patients and 1790 controls were included in the primary analysis. Additionally, 355 Lewy body disease patients assessed as having a high likelihood of clinical DLB based on neuropathological findings were included in secondary analysis. Seven pathogenic LRRK2 variants were assessed in patients, while 17 common LRRK2 exonic variants and 1 GWAS-nominated common LRRK2 PD-risk variant were evaluated for association with DLB.
  
  
  
  We identified carriers of 2 different pathogenic LRRK2 variants. One clinical DLB patient was a p.G2019S carrier, while in the pathological high likelihood DLB series there was one carrier of the p.R1441C mutation. However, examination of clinical records revealed the p.R1441C carrier to have PD with dementia. Evaluation of common variants did not reveal any associations with DLB risk after multiple testing adjustment. However, a non-significant trend similar to that previously reported for PD was observed for the protective p.N551K-R1398H-K1423K haplotype in the clinical DLB series (OR: 0.76, P = 0.061).
  
  
  
  LRRK2 does not appear to play a major role in DLB, however further study of p.G2019S and the p.N551K-R1398H-K1423K haplotype is warranted to better understand their involvement in determining DLB risk.
authors: Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USA.
authors: Michael G
authors: MG
authors: Heckman
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.|Department of Biology, University of North Florida, Jacksonville, Florida, USA.
authors: Alexandra I
authors: AI
authors: Soto-Ortolaza
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors: Monica Y Sanchez
authors: MYS
authors: Contreras
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors: Melissa E
authors: ME
authors: Murray
authors: Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
authors: Otto
authors: O
authors: Pedraza
authors: Division of Biomedical Statistics and Informatics, Mayo Clinic, Jacksonville, Florida, USA.
authors: Nancy N
authors: NN
authors: Diehl
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors: Ronald
authors: R
authors: Walton
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors: Catherine
authors: C
authors: Labbé
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors: Oswaldo
authors: O
authors: Lorenzo-Betancor
authors: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
authors: Ryan J
authors: RJ
authors: Uitti
authors: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
authors: Jay
authors: J
authors: van Gerpen
authors: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
authors: Nilüfer
authors: N
authors: Ertekin-Taner
authors: Department of Psychiatry and Psychology Mayo Clinic, Rochester, Minnesota, USA.
authors: Glenn E
authors: GE
authors: Smith
authors: Department of Radiology Mayo Clinic, Rochester, Minnesota, USA.
authors: Kejal
authors: K
authors: Kantarci
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Rodolfo
authors: R
authors: Savica
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors: David T
authors: DT
authors: Jones
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Jonathan
authors: J
authors: Graff-Radford
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors: David S
authors: DS
authors: Knopman
authors: Department of Radiology Mayo Clinic, Rochester, Minnesota, USA.
authors: Val J
authors: VJ
authors: Lowe
authors: Department of Radiology Mayo Clinic, Rochester, Minnesota, USA.
authors: Clifford R
authors: CR
authors: Jack
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Ronald C
authors: RC
authors: Petersen
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.|Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Joseph E
authors: JE
authors: Parisi
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors: Rosa
authors: R
authors: Rademakers
authors: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
authors: Zbigniew K
authors: ZK
authors: Wszolek
authors: Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
authors: Neill R
authors: NR
authors: Graff-Radford
authors: Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
authors: Tanis J
authors: TJ
authors: Ferman
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
authors: Dennis W
authors: DW
authors: Dickson
authors: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors: Bradley F
authors: BF
authors: Boeve
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.|Department of Biology, University of North Florida, Jacksonville, Florida, USA.|School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.|Mayo Graduate School, Mayo Clinic, Jacksonville, Florida, USA.
authors: Owen A
authors: OA
authors: Ross
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics*; D020961:Lewy Body Disease / Q000235:genetics* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: Dementia with Lewy bodies; Genetics; LRRK2; Parkinson's disease