title: Increased microRNA-34c abundance in Alzheimer's disease circulating blood plasma.
abstract: Circulating microRNAs, present either in the cellular component, peripheral blood mononuclear cells (PBMC), or in cell-free plasma, have emerged as biomarkers for age-dependent systemic, disease-associated changes in many organs. Previously, we have shown that microRNA (miR)-34a is increased in circulating PBMC of Alzheimer's disease (AD) patients. In the present study, we show that this microRNA's sister, miR-34c, exhibits even greater increase in both cellular and plasma components of AD circulating blood samples, compared to normal age-matched controls. Statistical analysis shows the accuracy of levels of miR-34c assayed by receiver operating characteristic (ROC) analysis: the area under the curve is 0.99 (p < 0.0001) and the 95% confidence level extends from 0.97 to 1. Pearson correlation between miR-34c levels and mild and moderate AD, as defined by the mini-mental state examination (MMSE), shows an r-value of -0.7, suggesting a relatively strong inverse relationship between the two parameters. These data show that plasma levels of microRNA 34c are much more prominent in AD than those of its sister, miR-34a, or than its own level in PBMC. Transfection studies show that miR-34c, as does its sister miR-34a, represses the expression of several selected genes involved in cell survival and oxidative defense pathways, such as Bcl2, SIRT1, and others, in cultured cells. Taken together, our results indicate that increased levels of miR-34c in both PBMC and plasma may reflect changes in circulating blood samples in AD patients, compared to age-matched normal controls.
authors.affiliation: Advanced Genomic Technology, LLC Louisville, KY, USA.
authors.forename: Shephali
authors.initials: S
authors.lastname: Bhatnagar
authors.affiliation: Department of Neurology and Neurosurgery, McGill University Montreal, QC, Canada ; Memory Clinic, Department of Medicine, Jewish General Hospital Montreal, QC, Canada ; Bloomfield Centre for Research in Aging, Lady Davis Institute Montreal, QC, Canada ; Division of Geriatric Medicine and Department of Clinical Neurosciences, Jewish General Hospital Montreal, QC, Canada.
authors.forename: Howard
authors.initials: H
authors.lastname: Chertkow
authors.affiliation: Department of Neurology and Neurosurgery, McGill University Montreal, QC, Canada ; Bloomfield Centre for Research in Aging, Lady Davis Institute Montreal, QC, Canada ; Division of Geriatric Medicine and Department of Clinical Neurosciences, Jewish General Hospital Montreal, QC, Canada.
authors.forename: Hyman M
authors.initials: HM
authors.lastname: Schipper
authors.affiliation: Advanced Genomic Technology, LLC Louisville, KY, USA.
authors.forename: Zongfei
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Advanced Genomic Technology, LLC Louisville, KY, USA.
authors.forename: Vikranth
authors.initials: V
authors.lastname: Shetty
authors.affiliation: Advanced Genomic Technology, LLC Louisville, KY, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Jenkins
authors.affiliation: Advanced Genomic Technology, LLC Louisville, KY, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Jones
authors.affiliation: Advanced Genomic Technology, LLC Louisville, KY, USA.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Wang
keywords: miR-34a; miR-34c; peripheral blood mononuclear cells (PBMC); plasma microRNA