Carlos Cruchaga, United States of America
Washington University School of Medicine PsychiatryModerator of 1 Session
Presenter of 2 Presentations
CIRCULAR RNAS ARE SIGNIFICANTLY ASSOCIATED WITH BOTH SYMPTOMATIC AND PRE-SYMPTOMATIC ALZHEIMER’S DISEASE
Abstract
Aims
Circular RNAs (circRNAs) are a class of RNAs highly expressed in the nervous system and enriched in synaptoneurosomes. A recent study suggest that circCDR1-as is downregulated in the frontal cortex of Alzheimer’s Disease (AD) patients. A study investigating whether other circRNAs are differentially expressed in the context of AD remains outstanding. Here, we conduct an analysis of circRNA expression to explore the relevance of circRNA expression in AD.
Methods
We generated RNA-seq data from 83 individuals with AD and 16 control individuals. We performed circRNA differential expression (DE) analysis on the basis of clinical dementia rating (CDR). We replicated the DE analyses using publically available superior temporal cortex RNA sequencing data from the Mount Sinai Brain Bank (173 AD cases and 63 controls) and performed a meta-analysis.
Results
On meta-analysis, we observed six circRNAs to be significantly DE on the basis of CDR. This included the previously reported circCDR1-as (p-value: 1.66×10-6), as well as five novel ones: circHOMER1 (p-value: 3.30×10-9), circDOCK1 (p-value: 4.17×10-9), circPEX5L (p-value: 6.12×10-6), circKCNN2 (p-value: 6.12 × 10-6), and circMLIP (p-value: 8.45 × 10-6). When included in a model with AD risk factors (number of APOE-4 alleles, gender, age at death, and ethnicity), the circRNAs collectively contributed more than 34% of the variation in CDR in our parietal dataset. In contrast, number of APOE-4 alleles, the most common genetic risk factor, only explained 9% of the variation in CDR. Multiple circRNAs are differentially expressed in AD brain tissues.
Conclusions
Together these circRNAs contribute substantially to the variation in CDR.
LIVE DISCUSSION