Elevation of Peripheral BDNF Promoter Methylation Predicts Conversion from Amnestic Mild Cognitive Impairment to Alzheimer's Disease: A 5-Year Longitudinal Study.
Epigenetic aberrations have been identified as biomarkers to predict the risk of Alzheimer's disease (AD). This study aimed to evaluate whether altered DNA methylation status of BDNF promoter could be used as potential epigenetic biomarkers for predicting the progression from amnestic mild cognitive impairment (aMCI) to AD. A total of 506 aMCI patients and 728 cognitively normal controls were recruited in the cross-sectional analyses. Patients (n = 458) from aMCI cohort were classified into two groups after 5-year follow-up: aMCI-stable group (n = 330) and AD-conversion group (n = 128). DNA methylation of BDNF promoter was detected by bisulfite-PCR amplification and pyrosequencing. The DNA methylation levels of CpG1 and CpG2 in promoter I and CpG5 and CpG6 in promoter IV of BDNF gene were significantly higher in the aMCI group than in the control group at baseline and also were increased in the conversion group compared with the non-conversion group at 5-year follow up time point. CpG5 in BDNF promoter IV had the highest AUC of 0.910 (95% CI: 0.817-0.983, p < 0.05). Kaplan-Meier analysis showed a significant AD conversion propensity for aMCI patients with high methylation levels of CpG5 (HR = 1.96, 95% CI: 1.07-2.98, p < 0.001). Multivariate Cox regression analysis revealed elevated methylation status of CpG5 was a significant independent predictor for AD conversion (HR = 3.51, p = 0.013). These results suggest that elevation of peripheral BDNF promoter methylation might be used as potential epigenetic biomarkers for predicting the conversion from aMCI to AD.
['Xie|Bing|B|', 'Xu|Yao|Y|', 'Liu|Zanchao|Z|', 'Liu|Wenxuan|W|', 'Jiang|Lei|L|', 'Zhang|Rui|R|', 'Cui|Dongsheng|D|', 'Zhang|Qingfu|Q|', 'Xu|Shunjiang|S|']
D000368:Aged D000369:Aged, 80 and over D000544:Alzheimer Disease D019540:Area Under Curve D019208:Brain-Derived Neurotrophic Factor D060825:Cognitive Dysfunction D015331:Cohort Studies D018899:CpG Islands D003430:Cross-Sectional Studies D019175:DNA Methylation D018450:Disease Progression D005260:Female D006801:Humans D053208:Kaplan-Meier Estimate D008297:Male D008875:Middle Aged D009483:Neuropsychological Tests D011401:Promoter Regions, Genetic D011569:Psychiatric Status Rating Scales D012044:Regression Analysis
BDNF promoter amnestic mild cognitive impairment DNA methylation Alzheimer’s disease follow-up study