An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations

the Dominantly Inherited Alzheimer Network (DIAN)

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA–AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)1903-1912
Number of pages10
JournalNature Neuroscience
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2019

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Atlases
Alzheimer Disease
RNA
MicroRNAs
Brain
RNA Sequence Analysis
Parietal Lobe
Genes
Dementia
Binding Sites
Messenger RNA
Research
circular RNA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations. / the Dominantly Inherited Alzheimer Network (DIAN).

In: Nature Neuroscience, Vol. 22, No. 11, 01.11.2019, p. 1903-1912.

Research output: Contribution to journalArticle

the Dominantly Inherited Alzheimer Network (DIAN). / An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations. In: Nature Neuroscience. 2019 ; Vol. 22, No. 11. pp. 1903-1912.
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abstract = "Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; ncontrol = 13; nAD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA–AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.",
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