The associations of APP, PSEN1, and PSEN2 genes with Alzheimer's disease: A large case-control study in Chinese population.

Aim: The associations of non-pathogenic variants of APP, PSEN1, and PSEN2 with Alzheimer's disease (AD) remain unclear. This study is aimed at determining the role of these variants in AD.

Methods: Our study recruited 1154 AD patients and 2403 controls. APP, PSEN1, PSEN2, and APOE were sequenced using a targeted panel. Variants were classified into common or rare variants with the minor allele frequencies (MAF) cutoff of 0.01. Common variant (MAF≥0.01)-based association test was performed by PLINK 1.9, and gene-based (MAF <0.01) association analysis was conducted using Sequence Kernel Association Test-Optimal (SKAT-O test). Additionally, using PLINK 1.9, we performed AD endophenotypes association studies.

Results: A common variant, PSEN2 rs11405, was suggestively associated with AD risk (p = 1.08 × 10 ). The gene-based association analysis revealed that the APP gene exhibited a significant association with AD (p = 1.43 × 10 ). In the AD endophenotypes association studies, APP rs459543 was nominally correlated with CSF Aβ42 level (p = 7.91 × 10 ).

Conclusion: Our study indicated that non-pathogenic variants in PSEN2 and APP may be involved in AD pathogenesis in the Chinese population.