An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.
Nat Neurosci
; 22(11): 1903-1912, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31591557
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Lobo Parietal
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Atlas como Assunto
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Perfilação da Expressão Gênica
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Doença de Alzheimer
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RNA Circular
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article