Analysis of the LRRK2 Gly2385Arg variant in Alzheimer's disease in Taiwan

Objective: To analyze the Gly2385Arg (G2385R) mutation in Taiwanese Alzheimer's disease (AD) patients. Background: The leucine-rich repeat kinase 2 (LRRK2) gene is well known to predispose subjects to Parkinson's disease (PD). The Gly2385Arg (G2385R) variant of LRRK2 is believed to be "East Asian"-specific, particularly in the Han Chinese population; however, whether the LRRK2 G2385R is associated with a risk of AD in pure Han-Chinese patients has not often been studied. Methods: A total of 209 AD patients (87 men, 122 women) and 180 age- and gender-matched controls were recruited and the demographic data of the AD patients were analyzed. Genotyping of the Gly2385Arg variant was studied using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Results: Subjects with the Gly2385Arg variant were all heterozygous carriers. The frequency of Gly2385Arg carriers did not differ significantly between the AD patients and controls (4.78% versus 4.44%, odds ratio = 1.04, 95% CI = 0.62-1.77, P = 0.87). In the AD patient group, the age of symptom onset, the length of education, or the MMSE score showed no significant differences between wild-type carriers and heterozygous variant carriers (P = 0.51, 0.43, and 0.09). Conclusion: The Gly2385Arg variant of LRRK2 may not be a major risk factor for AD in pure Han Chinese patient. Among the AD patients, Gly2385Arg carriers were not clinically different from wild-type carriers.