Objective To investigate the role of protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) in the pathogenic process of Alzheimer's disease (AD).Methods The expression of POMGnT1 gene was examined in AD model cells (N2a/amyloid-precursor protein (APP) 695swe,n=3) and N2a/wt cells (n=3) using real-time PCR and Western blotting.This expression was also examined in AD model mice (APP/PS1,n=3) and wild-type mice (n=3) using immunofluorescence staining.Amyloid β-protein (Aβ) were examined in POMGnT1-gene-knockout mice (n=3) and wild-type mice (n=3) using immunochemistRy.Results The expression of POMGnT1 gene decreased in mRNA and protein levels in N2a/APP695swe cells compared to N2a/wt cells (mRNA:0.80±0.02 vs 1.00,t=10.52,P＜0.01;protein:0.50±0.02 vs 1.31±0.04,t=18.64,P＜0.01).Immunofluorescence results showed the reduced expression of POMGnT1 protein in neurons of APP/PS1 mice.Immunochemistry results showed more Aβ deposits in POMGnT1-gene-knockout mice (2 months old:0.358±0.014 vs 0.048±0.001,t=22.58,P＜0.01;1 year old:0.266±0.004 vs 0.229±0.003,t=7.771,P=0.002).Conclusion These findings suggest POMGnT1 gene may play an important role in the pathogenic process of AD.