Background: Although β-amyloid (Aβ) degradation has been normally implicated in the
pathogenesis of late-onset Alzheimer’s disease (LOAD) through cellular biological studies, the
genetic studies linking Aβ degradation and LOAD are still scarce. Neprilysin (NEP), one of the
most crucial Aβ-degrading enzymes in AD, is the metalloendopeptidase which particularly participates
in the monomeric Aβ species degradation. MicroRNAs (miRNAs) exert post-transcriptional
dysregulation and their target sequence on the 3’ untranslated regions (3’UTR) may be regulated by
single nucleotide polymorphisms (SNPs).
Objective: To investigate the potential risk of common locus within NEP gene (MME) with LOAD
in Northern Han Chinese population.
Method: We screened a locus (rs6665) in 3’ UTR of NEP gene (MME) which sequence was
specially regulated by miRNA-187, and further investigated its possible association with LOAD
onset in a large case-control study (984 LOAD patients and 1354 healthy controls) in Northern Han
Results: The distribution of rs6665 genotype (P=0.003) and allele A/C (P=0.001) showed significant
difference between LOAD and controls (Odds Ratio (OR) =1.255, 95% Confidence Interval
(CI) =1.102-1.429). After adjusting for age, gender and Apolipoprotein (ApoE) ε4 status, the minor
C allele of rs6665 showed significant association with LOAD in all three genotypic models (Dominant:
P=0.003, OR=1.291, 95%CI=1.092-1.526; Recessive: P=0.030, OR =1.425, 95%CI =1.035-
1.961; Additive: P=0.001, OR=1.249,95%CI=1.093-1.427). After stratifying by ApoE ε4 status,
rs6665 polymorphism was found to elevate the LOAD risk in ApoE ε4 carriers (P=0.002,
Conclusion: Our study firstly confirmed the association of MME miRNA binding site polymorphism
with the risk of LOAD. However, the association results warrant further validation.