The effects of coagulation factors on the risk of Alzheimer's disease: A Mendelian randomization study.

Background: Observational studies indicate a complex relationship between coagulation factors and Alzheimer's disease (AD). However, the current findings are inconsistent, and it remains uncertain whether a causal relationship exists.

Objective: This study utilizes a Mendelian randomization analysis to investigate the causal relationships between blood levels of coagulation factors and AD risk.

Methods: Eleven coagulation factors with valid instrumental variables available were evaluated. Two independent cohorts of European ancestry with AD genome-wide association study (GWAS) summary statistics were used: UK Biobank (UKB, N = 472,868) and the International Genomics of Alzheimer's Project (IGAP, N = 63,926). We primarily conducted Mendelian randomization (MR) analyses using the Inverse variance weighted (IVW). Meanwhile, the MR-Egger intercept test is used to detect horizontal pleiotropy, the Residual Sum of Squares observed (RSSobs) is used to assess the model's goodness of fit, and the leave-one-out analysis is employed for sensitivity analysis.

Results: Using IVW analysis, the UKB database shows positive correlations of Protein C (PC, p = 0.002), Activated Partial Thromboplastin Time (aPTT, p = 0.019), and coagulation factor X (FX, p = 0.032) with AD, and a negative association for coagulation factor XI (FXI, p = 0.021). The IGAP database mirrors these findings for PC and FXI but not for the others. Leave-one-out analysis showed an anomaly after a single single nucleotide polymorphism (SNP) driving, yet the overall results remained stable.

Conclusions: This study demonstrates that elevated levels of PC, FX, and aPTT, along with reduced levels of FXI, are causally associated with an increased risk of AD. These findings might pave the way for the diagnosis and treatment of AD.