title: LRRK2 variant associated with Alzheimer's disease.
abstract: Overlapping neurodegenerative pathologies (including Alzheimer's disease, AD) have been described in Parkinson's disease (PD) patients with leucine-rich repeat kinase-2 (LRRK2) mutations. We analyzed a LRRK2 PD (R1628P) risk variant in a group of 885 subjects comprising of AD and controls. The frequency of the R1628P allele was higher in AD compared to controls (3.5% vs. 1.6%, OR 2.3, 95 CI 1.2-4.4, p=0.018). In vitro, the mean percentage of apoptosis and cell death observed for the R1628P transfected human cell lines was higher compared to wild type 21.8 ± 1.9, vs. 17.1 ± 1.3, p<0.05, 30.2 ± 2.2 vs. 25.7 ± 1.3, p<0.05). The LRRK2 R1628P variant increases the risk of AD in our population and our in vitro findings suggest that it is a functional variant and predisposes to apoptosis.
authors.affiliation: Department of Neurology, Clinical Research and Health Screening, Singapore General Hospital, Singapore.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: P
authors.initials: P
authors.lastname: Ho
authors.forename: Yuen
authors.initials: Y
authors.lastname: Yih
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: W L
authors.initials: WL
authors.lastname: Lee
authors.forename: E K
authors.initials: EK
authors.lastname: Tan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014162:Transfection
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases