摘要
Background:MicroRNAs(miRNAs)are small non-coding RNA molecules that function as posttranscriptional regulators of gene expression.Measurements of miRNAs in cerebrospinal fluid(CSF)and blood have just started gaining attention as a novel diagnostic tool for various neurological conditions.The purpose of this exploratory investigation was to analyze the expression of miRNAs in CSF and blood of patients with Alzheimer’s disease(AD)and other neurodegenerative disorders in order to identify potential miRNA biomarker candidates able to separate AD from other types of dementia.Methods:CSF was collected by lumbar puncture performed on 10 patients diagnosed with AD and 10 patients diagnosed with either vascular dementia,frontotemporal dementia or dementia with Lewy bodies.Blood samples were taken immediately after.Total RNA was extracted from cell free fractions of CSF and plasma,and a screening for 372 known miRNA sequences was carried out by real time quantitative polymerase chain reactions(miRCURY LNA™Universal RT miRNA PCR,Polyadenylation and cDNA synthesis kit,Exiqon).Results:Fifty-two miRNAs were detected in CSF in at least nine out of ten patients in both groups.Among these,two miRNAs(let-7i-5p and miR-15a-5p)were found significantly up-regulated and one miRNA(miR-29c-3p)was found significantly down-regulated in patients with AD compared to controls.One hundred and sixty-eight miRNAs were frequently detected in the blood,among which miR-590-5p and miR-142-5p were significantly up-regulated and miR-194-5p was significantly down-regulated in AD patients compared to controls.Conclusions:Detection of miRNA expression profiles in blood and in particular CSF of patients diagnosed with different types of dementia is feasible and it seems that several expressional differences between AD and other dementia types do exist when measured in a clinically relevant setup.In this explorative pilot study,the deregulated miRNAs in CSF of AD patients may be associated with relevant target genes related to AD pathology,including A
基金
This project was supported by grants from the Research Foundation of Nordsijallands Hospital,the Research Foundation for Health Research of the Capital Region of Denmark,and Helen Rude's Foundation.
