Association Of PLD3 Gene Polymorphism With Alzheimer 's Disease Amyloid Phenotype

Objective: To explore the association of the phospholipase D3(PLD3) gene with amyloid-related phenotypes in Alzheimer’s disease(AD)METHODS: A total of 281 normal cognition(NC),483 mild cognitive impairment(MCI) individuals and 48 AD from the Alzheimer’s disease Neuroimaging Initiative(ADNI) database is included in our analysis. Multiple linear regression models were applied to examine the association between thirteen single nucleotide polymorphisms(SNPs) with amyloid-related phenotypes.RESULTS: No statistical differences were observed among NC, MCI and AD patients when comparing the distribution of all the tested SNPs allele frequencies in our study.rs11667768 was significant associated with CSF Aβ1-42 level in the NC group(p=0.00048, pc=0.006). For rs11667768, minor allele carriers showing higher CSF Aβ1-42 levels in a dose-dependent manner. Moreover, we observed some nominal associations between 3 SNPs(rs11667768, rs11666860 and rs62107640) and CSF Aβ1-42 levels in the MCI group(p=0.037, p=0.045 and p=0.035, respectively). However, no association remained statistically significant after Bonferroni correction. Regarding the AV45-PET analysis, we did not observe any association of all SNPs with florbetapir retention in four main regions(frontal, angerior/posterior cingulate, lateral parietal, lateral temporal), as well as the cortical SUVR in all groups.CONCLUSION: we have found one PLD3 variant(rs11667768) associated with amyloid burden detected by CSF Aβ1–42 level in normal individuals, suggesting the potential role of PLD3 in Aβ pathology.