Association between Presenilin 1 gene methylation and sporadic Alzheimer's disease / 中华老年医学杂志

ABSTRACT

Objective To investigate the correlation between Presenilin 1 gene methylation (PSEN1) and sporadic Alzheimer's disease (SAD).Methods Massarray method was used to perform an analysis of DNA methylation in the promoters of PSEN1 gene in lymphocytes from 35 SAD patients,33 mild cognitive impaired (MCI)patients and 22 age-and gender-matched controls.Reporter gene plasmid of PSEN1 was built by genetic recombination methods,and then transiently transfected into the SH-SY5Y and HeLa cells.After that,cells were treated with several agents including serum deprivation,Aβ25-35,5-aza-2'-deoxycytidine (5-aza Cdr) and S-adenosyl-Lmethionine (SAM).A dual-luciferase reporter assay system was used to calculate the relative luciferase activity (RLA).Results Some CpG sites of PSEN1 (Cytosines at-173,95 and +76) showed hypomethylation patterns in SAD cases as compared with MCI and control group (P＜0.01).A dual-luciferase reporter assay showing significant differences in PSEN1 transcription activities were found in both cell lines under SAM treatment [SY5Y,SAM(6.40±0.81),control(9.13±1.67),P=0.000; Hela,SAM(2.06±0.34),control(2.99±0.59),P=0.000].Conclusions DNA hypomethylation of PSEN1 gene promoter is significantly associated with SAD susceptibility.PSEN1 may change the gene transcription level by methylation,further affecting the activity of amyloid protein-like γ-secretase,leading to the onset of AD.