title: Increased frequency of the LRRK2 G2019S mutation in an elderly Ashkenazi Jewish population is not associated with dementia.
abstract: Mutations in leucine-rich repeat kinase 2 gene (LRRK2) have been associated with idiopathic Parkinson's disease (PD), as well as pleomorphic neurodegenerative pathology, including Alzheimer's disease. One specific LRRK2 mutation, G2019S, was reported in 18% of people with PD of Ashkenazi descent, supporting a founder effect in this population. To determine if this mutation is also associated with dementia in the Ashkenazim, we screened 192 elderly Ashkenazi Jewish (AJ) individuals in a longitudinal aging and cognition study, of whom 49 (25.5%) had dementia. Two non-demented individuals harbored the mutation (2/143, 1.4%), but no individuals with dementia. Neither person with the mutation had Parkinson's disease. Therefore, the LRRK2 mutation has a relatively high frequency in the AJ population, is not fully penetrant for parkinsonism in the elderly, and does not appear to be commonly associated with late-onset dementia.
authors.affiliation: Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, United States. rsaunder@bethisraelny.org
authors.forename: Rachel
authors.initials: R
authors.lastname: Saunders-Pullman
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lipton
authors.forename: Geetha
authors.initials: G
authors.lastname: Senthil
authors.forename: Mindy
authors.initials: M
authors.lastname: Katz
authors.forename: Camille
authors.initials: C
authors.lastname: Costan-Toth
authors.forename: Carol
authors.initials: C
authors.lastname: Derby
authors.forename: Susan
authors.initials: S
authors.lastname: Bressman
authors.forename: Joe
authors.initials: J
authors.lastname: Verghese
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
mesh_terms: D000369:Aged, 80 and over; D000375:Aging; D004252:DNA Mutational Analysis / Q000379:methods; D003704:Dementia / Q000235:genetics*; D005260:Female; D005998:Glycine / Q000235:genetics*; D006801:Humans; D007585:Jews / Q000208:ethnology / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012111:Residence Characteristics; D012694:Serine / Q000235:genetics*
chemical_list: D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine