Role of the TLR4 rs4986791 Polymorphism in the Development of Lateonset Alzheimer Disease and its Relationship with APOE*4

Objective: Based on that the association of the e4 allele of the APOE gene with the development of late-onset AD is one of the strongest and that TLR4 has been involved in AD pathogenesis. The aim of the present work was to study the role of rs4986791 polymorphism of the TLR4 gene in the development of AD and correlate any such association with the presence of allele e4 of the APOE gene. Methods: We included 161 unrelated Venezuelan subjects classified as either AD patients (n=61) or healthy individuals (n=100). Polymorphisms of TLR4 and APOE genes were identified with PCR-SSP and PCR-RFLP, respectively. Results: The rs4986791 polymorphism does not appear to be related to AD, although the presence of the CC genotype and the C allele apparently confers three times higher risk of developing AD. Finally, positive and negative associations among the combinations TLR4 /APOE genes and AD were observed. Conclusion: The results suggest the absence of any association between rs4986791 polymorphism of TLR4 gene and susceptibility to AD and the association of the e4 allele of the APOE gene with the development of this pathology was confirmed.