Curtis Ebl, United States of America
Washington University in St. Louis PsychiatryAuthor Of 1 Presentation
DNA METHYLATION IN AUTOSOMAL DOMINANTLY INHERITED AND SPORADIC ALZHEIMER DISEASE BRAINS
Abstract
Aims
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with many biological processes, and molecular changes. The etiology of AD is complex and not specific to a single genetic factor. Epigenetic changes could help explain the missing heritability not capture in GWAS chips and determine functional variants in genome-wide significant loci.
Methods
Our discovery cohort includes 477 post-mortem brains, 452 AD and 25 controls from Knight-ADRC and Dominantly Inherited Alzheimer Network cohorts. Our study included late-onset (LOAD), but also subjects with Mendelian mutations in APP, PSEN1 and PSEN2 genes (Autosomal Dominant AD; ADAD) and controls. We performed a genome-wide methylation study using DNA from parietal cortex. We used Infinium MethylationEPIC Beadchip arrays (Illumina) to measure DNA methylation. All statistical analyses were adjusted for sex, age at death and neuron proportion.
Results
Completion of this project will provide an enhanced characterization of the epigenetic factors associated with AD etiology. This data will also be integrated with RNA-seq data from the same samples to bring clarification in the interconnections between molecular layers and disrupted pathways involved in AD pathology. This study will enhance the understanding of the molecular dynamics underlying the pathophysiology of AD, and may lead to novel clues for its early detection, prevention and treatment.
Conclusions
Epigenetics of AD brains have been previously studied, but this is the first study to analyze both LOAD and ADAD. These results will be presented in the conference.