PT - JOURNAL ARTICLE AU - Ellis Patrick AU - Sathyapriya Rajagopal AU - Hon-Kit Andus Wong AU - Cristin McCabe AU - Jishu Xu AU - Anna Tang AU - Selina H. Imboywa AU - Julie A. Schneider AU - Nathalie Pochet AU - Anna M. Krichevsky AU - Lori B. Chibnik AU - David A. Bennett AU - Philip L. De Jager TI - Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer’s disease AID - 10.1101/095067 DP - 2016 Jan 01 TA - bioRxiv PG - 095067 4099 - http://biorxiv.org/content/early/2016/12/17/095067.short 4100 - http://biorxiv.org/content/early/2016/12/17/095067.full AB - Background Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer’s disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer’s disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region.Results We report analyses of expression profiling of miRNA (n=700 subjects) and lincRNA (n=540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging. Evaluating well-established (miR-132, miR-129), we confirm their association with pathologic AD in our dataset, and then characterize their in disease role in terms of neuritic β-amyloid plaques and neurofibrillary tangle pathology. Additionally, we identify one new miRNA (miR-99) and four lincRNA that are associated with these traits. Many other previously reported associations of microRNA with AD are associated with the confounders quantified in our longitudinal cohort. Finally, by performing analyses integrating both miRNA and RNA sequence data from the same individuals (525 samples), we characterize the impact of AD associated miRNA on human brain expression: we show that the effects of miR-132 and miR-129-5b converge on certain genes such as EP300 and find a role for miR200 and its target genes in AD using an integrated miRNA/mRNA analysis.Conclusions Overall, miRNAs play a modest role in human AD, but we observe robust evidence that a small number of miRNAs are responsible for specific alterations in the cortical transcriptome that are associated with AD.