Increased frequency of the LRRK2 G2019S mutation in an elderly Ashkenazi Jewish population is not associated with dementia.
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.
Saunders-Pullman
Rachel
R
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, United States. rsaunder@bethisraelny.org
Lipton
Richard B
RB
Senthil
Geetha
G
Katz
Mindy
M
Costan-Toth
Camille
C
Derby
Carol
C
Bressman
Susan
S
Verghese
Joe
J
Ozelius
Laurie J
LJ
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*
D012694:Serine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D005998:Glycine