Genome-wide profiling of circulatory microRNAs associated with cognition and dementia

Introduction MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Their role in the pathophysiology of dementia and potential as biomarkers remains undetermined. Methods We conducted a single- (one-by-one) and multi-marker (joint) analysis to identify well-expressed circulating miRNAs in plasma (total = 591) associated with general cognition and incident dementia, for 1615 participants of the population-based Rotterdam Study. Results During single-marker analysis, 47 miRNAs were nominally (P <= .05) associated with cognition and 18 miRNAs were nominally associated with incident dementia, after adjustment for potential confounders. Three miRNAs were common between cognition and dementia (miR-4539, miR-372-3p, and miR-566), with multi-marker analysis revealing another common miRNA (miR-7106-5p). In silico analysis of these four common miRNAs led to several putative target genes expressed in the brain, highlighting the mitogen-activated protein kinase signaling pathway. Discussion We provide population-based evidence on the relationship between circulatory miRNAs with cognition and dementia, including four common miRNAs that may elucidate downstream mechanisms. HIGHLIGHTS MicroRNAs (miRNAs) are involved in the (dys)function of the central nervous system. Four circulating miRNAs in plasma are associated with cognition and incident dementia. Several predicted target genes of these four miRNAs are expressed in the brain. These four miRNAs may be linked to pathways underlying dementia. Although miRNAs are promising biomarkers, experimental validation remains essential.

Automated summary

We conducted a study to identify circulating miRNAs in plasma associated with cognition and incident dementia. Four miRNAs were found to be commonly associated with both cognition and dementia, and their target genes were expressed in the brain, suggesting their potential involvement in dementia pathways.