The LRRK2 R 1628 P Variant Plays a Protective Role in H an C hinese Population with A lzheimer's Disease

Summary Aims A lzheimer's disease ( AD ) and P arkinson's disease ( PD ) are the most prevalent neurodegenerative disorders that may share some overlapping etiologies. Mutations within leucine‐rich repeat kinase 2 ( LRRK2 ) have been reported to be responsible for PD , and the location of LRRK2 is within a linkage peak for sporadic AD ( SAD ). The aim of this study was to investigate two A sian‐specific LRRK 2 variants, R 1628 P and G 2385 R , with the association of H an C hinese SAD . Methods Genotyping of R 1628 P and G 2385 R was performed by PCR ‐restriction fragment length polymorphism ( RFLP ) analysis in 390 patients with SAD and 545 unrelated age‐ and sex‐matched healthy controls. Results The frequency of the C allele within R 1628 P was more than three times higher in control group (1.7%) than in patients with SAD (0.5%) ( OR 0.264; 95% CI , 0.088–0.792, P  = 0.018). After stratification by the presence of one or two apolipoprotein E ε4 alleles, the protective effect becomes stronger (ε44: OR 0.028; 95% CI , 0.003–0.303, P  = 0.003; ε4: OR 0.104; 95% CI , 0.013–0.818, P  = 0.031). However, no difference was found in G 2385 R variant. Conclusion Our study suggested that R 1628 P variant within LRRK2 plays a protective role in H an C hinese population with SAD and such effect has an interaction with the APOE genotype.