Abstract
Objective: To describe RNA editing patterns in blood specimens of African American (AA) and Non-Hispanic White (NHW) Alzheimer’s Disease (AD) cases and controls. Background: A-to-I RNA editing is the post-transcriptional, enzyme-mediated process by which individual Adenosine bases in double-stranded mRNA are deaminated to Inosine. RNA editing contributes to various biological processes including neuronal development and immune regulation, and editing deficiencies have been observed in AD hippocampi. Given the role of the adaptive immune system in the pathogenesis of AD, we pursued the first large scale study describing AD associated changes of RNA editing in blood. Historically, genetic studies of AD have focused primarily on NHW, but here we broaden our functional genomics efforts to include AA individuals in order to identify ethnicity-specific editing signatures in these diverse populations. Design/Methods: Whole transcriptome RNA sequencing was performed on peripheral blood specimens from 60 AD cases (30 AA, 30 NHW) and 60 age, ethnicity, and sex-matched controls. REDItools software was used to identify candidate editing events, and the output was filtered for quality. Results: A total of 345735 A-to-I events were detected at 29246 unique sites across all individuals. Consistent with existing literature, 53% of editing events were of the canonical A-to-I type, 62% of A-to-I edits were found in non-coding regions, and 77% of A-to-I events had previously been reported in the RADAR and DARNED databases. Globally, cases had fewer A-to-I events per individual than controls (mean=2562 vs. 3201, median=1693 vs. 2701, p=0.05). No significant difference was found in the global number of editing events between AA’s and NHW’s or between Males and Females. Conclusions: AD cases of both NHW and AA ethnicities have lower global levels of RNA editing in blood than controls. This may be evidence of a post-transcriptional program contributing to the underlying complexity of AD pathophysiology. Study Supported by: This study is supported by a supplement to the NIA grant “Replication and Extension of ADSP Discoveries in African-Americans” U01AG052410-01. Disclosure: Dr. Gardner has nothing to disclose. Dr. Griswold has nothing to disclose. Dr. Sivasankaran has nothing to disclose. Dr. Rajabi has nothing to disclose. Dr. Kunkle has nothing to disclose. Dr. Hamilton has nothing to disclose. Dr. Jaworski has nothing to disclose. Dr. Bush has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Beecham has nothing to disclose. Dr. Byrd has nothing to disclose. Dr. Haines has nothing to disclose. Dr. Pericak-Vance has nothing to disclose.