Genetic Association Analysis between TDP-43 Polymorphisms and Alzheimer’s Disease in a Japanese Population

Abstract

Background/Aims: A recent paper reported that the TAR-DNA binding protein (TDP-43) is the disease protein in amyotrophic lateral sclerosis and frontotemporal lobar dementia with ubiquitin-positive inclusions. In addition, it has been shown that TDP-43 may play a role in the pathogenesis of Alzheimer’s disease (AD). This study aims to investigate whether single nucleotide polymorphisms (SNPs) of the TDP-43 gene are associated with AD. Methods: Eight SNPs, genotyped using TaqMan technology, were analyzed using a case-control study design including a haplotype analysis. Furthermore, an analysis of the cases divided according to apolipoprotein E (APO E) status was also carried out. Our case-control dataset consists of 181 AD patients and 130 age-matched controls. Results: Although none of the SNPs showed statistically significant association, we identified an association between a specific haplotype (G-A-A-G) of the TDP-43 gene and risk for AD. We could not confirm any synergetic association between the SNPs and APO E in our AD patients. Despite the relatively small sample size, our results indicate a possible genetic association between TDP- 43 and AD. Conclusion: Further genetic studies are needed to clarify the relationship between the TDP-43 gene and AD.