Differential Methylation in <i>APOE</i> (Chr19; Exon Four; from 44,909,188 to 44,909,373/hg38) and Increased Apolipoprotein E Plasma Levels in Subjects with Mild Cognitive Impairment

• Main Authors: Oscar Mancera-Páez, Kelly Estrada-Orozco, María Fernanda Mahecha, Francy Cruz, Kely Bonilla-Vargas, Nicolás Sandoval, Esneyder Guerrero, David Salcedo-Tacuma, Jesús D. Melgarejo, Edwin Vega, Jenny Ortega-Rojas, Gustavo C. Román, Rodrigo Pardo-Turriago, Humberto Arboleda
• Format: Article
• Language: English
• Published: MDPI AG 2019-03-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>APOE</i> gene; apolipoprotein E; DNA methylation; mild cognitive impairment; Hispanics
• Online Access: https://www.mdpi.com/1422-0067/20/6/1394

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the <i>APOE</i> gene and apolipoprotein E (ApoE) plasma levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: In total, 100 participants were included (71% women; average age, 70 years; range, 43&#8211;91 years). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Using multivariate logistic regression models adjusted by age and gender, we examined the risk association of MCI with plasma ApoE and <i>APOE</i> methylation. Results: MCI was diagnosed in 41 subjects (average age, 66.5 &#177; 9.6 years) and compared with 59 controls. Elevated plasma ApoE and <i>APOE</i> methylation of CpGs 165, 190, and 198 were risk factors for MCI (<i>p</i> &lt; 0.05). Higher CpG-227 methylation correlated with lower risk for MCI (<i>p</i> = 0.002). Only CpG-227 was significantly correlated with plasma ApoE levels (correlation coefficient = &#8722;0.665; <i>p</i> = 0.008). Conclusion: Differential <i>APOE</i> methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns require confirmation in larger samples but could potentially be used as biomarkers to identify early stages of MCI.