Abstract
BackgroundMicroRNAs (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.MethodsCSF 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).ResultsFifty-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.ConclusionsDetection 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 APP and BACE1, which suggests that miRNAs are interesting candidates for AD biomarkers in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s40035-016-0053-5) contains supplementary material, which is available to authorized users.
Highlights
MicroRNAs are small non-coding RNA molecules that function as posttranscriptional regulators of gene expression
227 miRNAs occurred in both cerebrospinal fluid (CSF) and blood, 81 miRNAs occurred in blood only, and a minor proportion of 4 miRNAs was found exclusively in the CSF
When examining the expression of miR-225p, miR-199b-5p and miR-206 we found no association between the expression of these miRNAs in the blood and CSF of patients with an elevated albumin CSF/serum concentration quotient (Qalb), suggesting that their presence in CSF does not seem to be explained by a leak in blood–brain barrier (BBB)
Summary
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. Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder characterized by cognitive impairment and neuropsychiatric symptoms leading to restrictions in the activities of daily living. The complex neurobiology of AD, which is not fully understood, includes the development of extracellular amyloid plaques and intracellular neurofibrillary tangles, vascular changes, neuronal inflammation, neurochemical changes, and progressive brain atrophy [4,5,6,7].
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