The potential of microRNAs as biofluid markers of neurodegenerative diseases – a systematic review

Abstract MicroRNAs (miRNA) are biological molecules transcribed from non-protein coding regions of the genome, participating in regulating cellular processes. MiRNAs in biofluids may possess neurodegenerative disease biomarker potential for screening tests, differential diagnosis and disease progression monitoring. This systematic review clarifies biomarker potential of miRNAs detected in biofluids of neurodegenerative disease patients. Thirty-three and ten miRNAs displayed significant expression between patients with multiple sclerosis and Alzheimer's disease, respectively, compared to healthy controls in minimum two studies. Thirty-eight miRNAs showed biomarker potential by distinguishing significantly between minimum two diseases. Summarized data directs future research towards discovering new biomarkers for neurodegenerative diseases.

[1]  S. Hébert,et al.  Alterations of the microRNA network cause neurodegenerative disease , 2009, Trends in Neurosciences.

[2]  Kira S. Sheinerman,et al.  Circulating cell-free microRNA as biomarkers for screening, diagnosis and monitoring of neurodegenerative diseases and other neurologic pathologies , 2013, Front. Cell. Neurosci..

[3]  F. Peruzzi,et al.  Cerebrospinal fluid miRNA profile in HIV‐encephalitis , 2013, Journal of cellular physiology.

[4]  L. Kappos,et al.  Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects. , 2012, Clinical immunology.

[5]  Fei Chen,et al.  Effect of microRNA‐34a in cell cycle, differentiation, and apoptosis: A review , 2012, Journal of biochemical and molecular toxicology.

[6]  Zhongdang Xiao,et al.  Aberrant expression of serum miRNAs in schizophrenia. , 2012, Journal of psychiatric research.

[7]  A. Malhotra,et al.  In Vivo MicroRNA Detection and Quantitation in Cerebrospinal Fluid , 2012, Journal of Molecular Neuroscience.

[8]  M. Hecker,et al.  Integration of MicroRNA Databases to Study MicroRNAs Associated with Multiple Sclerosis , 2012, Molecular Neurobiology.

[9]  B. De Felice,et al.  A miRNA signature in leukocytes from sporadic amyotrophic lateral sclerosis. , 2012, Gene.

[10]  Yibin Kang,et al.  A one-two punch of miR-126/126* against metastasis , 2013, Nature Cell Biology.

[11]  E. Kroh,et al.  Blood Cell Origin of Circulating MicroRNAs: A Cautionary Note for Cancer Biomarker Studies , 2011, Cancer Prevention Research.

[12]  Aikaterini S. Papadopoulou,et al.  MicroRNA-29 in the adaptive immune system: setting the threshold , 2012, Cellular and Molecular Life Sciences.

[13]  M. Prince,et al.  Epidemiology of dementias and Alzheimer's disease. , 2012, Archives of medical research.

[14]  P. Sørensen,et al.  Differential microRNA expression in blood in multiple sclerosis , 2013, Multiple sclerosis.

[15]  E. Kroh,et al.  Plasma Processing Conditions Substantially Influence Circulating microRNA Biomarker Levels , 2013, PloS one.

[16]  Jiuhong Kang,et al.  MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis , 2009, Nature Immunology.

[17]  O. Suchowersky,et al.  Tauopathies: One Disease or Many? , 2011, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[18]  Ferdinando Di Cunto,et al.  Coding-Independent Regulation of the Tumor Suppressor PTEN by Competing Endogenous mRNAs , 2011, Cell.

[19]  N. Bresolin,et al.  Role of hnRNP-A1 and miR-590-3p in neuronal death: genetics and expression analysis in patients with Alzheimer disease and frontotemporal lobar degeneration. , 2011, Rejuvenation Research.

[20]  R. Hohlfeld,et al.  The emerging role of microRNAs in multiple sclerosis , 2011, Nature Reviews Neurology.

[21]  P. Dash,et al.  Human traumatic brain injury alters plasma microRNA levels. , 2010, Journal of neurotrauma.

[22]  K. Weigelt,et al.  Down-regulation of inflammation-protective microRNAs 146a and 212 in monocytes of patients with postpartum psychosis , 2013, Brain, Behavior, and Immunity.

[23]  Wu-xian Li,et al.  Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus. , 2012, Translational research : the journal of laboratory and clinical medicine.

[24]  M. Prince,et al.  World Alzheimer Report 2013 , 2014 .

[25]  T. Yokota,et al.  Circulating microRNAs in the cerebrospinal fluid of patients with brain diseases. , 2013, Methods in molecular biology.

[26]  A. Bizzi,et al.  Sporadic human prion diseases: molecular insights and diagnosis , 2012, The Lancet Neurology.

[27]  J. A. Lozano,et al.  Differential Micro RNA Expression in PBMC from Multiple Sclerosis Patients , 2009, PloS one.

[28]  A. Roses,et al.  Identification of miRNA Changes in Alzheimer's Disease Brain and CSF Yields Putative Biomarkers and Insights into Disease Pathways , 2008 .

[29]  Xuemei Chen,et al.  Regulation of small RNA stability: methylation and beyond , 2012, Cell Research.

[30]  Jessica A. Weber,et al.  The microRNA spectrum in 12 body fluids. , 2010, Clinical chemistry.

[31]  G. Meister,et al.  Regulation of microRNA biogenesis and function , 2012, Thrombosis and Haemostasis.

[32]  L. Bally-Cuif,et al.  MicroRNAs in brain development and physiology , 2009, Current Opinion in Neurobiology.

[33]  Woong-Yang Park,et al.  miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1 , 2011, Experimental & Molecular Medicine.

[34]  T. Dawson,et al.  MicroRNA-223 is neuroprotective by targeting glutamate receptors , 2012, Proceedings of the National Academy of Sciences.

[35]  M. Atiya,et al.  Glatiramer Acetate Treatment Normalizes Deregulated microRNA Expression in Relapsing Remitting Multiple Sclerosis , 2011, PloS one.

[36]  R. Gold,et al.  Regulated microRNAs in the CSF of patients with multiple sclerosis , 2012, Neurology.

[37]  S. Lawler,et al.  Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. , 2011, Brain : a journal of neurology.

[38]  R. Gold,et al.  Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. , 2011, Blood.

[39]  E. Chan,et al.  MicroRNA-146a in autoimmunity and innate immune responses , 2012, Annals of the rheumatic diseases.

[40]  Mathew B. Cox,et al.  MicroRNAs miR-17 and miR-20a Inhibit T Cell Activation Genes and Are Under-Expressed in MS Whole Blood , 2010, PloS one.

[41]  G. Calin,et al.  MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases. , 2009, Expert opinion on biological therapy.

[42]  V. Martinelli,et al.  MicroRNA and mRNA expression profile screening in multiple sclerosis patients to unravel novel pathogenic steps and identify potential biomarkers , 2012, Neuroscience Letters.

[43]  R. Malenka,et al.  An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration , 2012, Nature Neuroscience.

[44]  L. Kappos,et al.  Altered expression of miR‐17‐5p in CD4+ lymphocytes of relapsing–remitting multiple sclerosis patients , 2010, European journal of immunology.

[45]  Christina Backes,et al.  Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing , 2014, Multiple sclerosis.

[46]  N. Schonrock,et al.  MicroRNA networks surrounding APP and amyloid-β metabolism — Implications for Alzheimer's disease , 2012, Experimental Neurology.

[47]  S. Dimmeler,et al.  MicroRNAs in age-related diseases , 2013, EMBO molecular medicine.

[48]  E. Martin,et al.  Convergence of miRNA Expression Profiling, α-Synuclein Interacton and GWAS in Parkinson's Disease , 2011, PloS one.

[49]  S. Pastorino,et al.  MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. , 2012, Neuro-oncology.

[50]  A. Junker.  Pathophysiology of translational regulation by microRNAs in multiple sclerosis , 2011, FEBS letters.

[51]  M. Mullan,et al.  Plasma microRNA biomarkers for detection of mild cognitive impairment , 2012, Aging.

[52]  W. Lukiw,et al.  Spreading of Alzheimer's disease inflammatory signaling through soluble micro‐RNA , 2012, Neuroreport.

[53]  R. Margis,et al.  Identification of blood microRNAs associated to Parkinsonĭs disease. , 2011, Journal of biotechnology.

[54]  A. Salviati,et al.  Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients , 2011, International journal of molecular sciences.

[55]  M. Verbeek,et al.  MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid , 2014, Neurobiology of Aging.

[56]  G. Crabtree,et al.  MicroRNAs: regulators of neuronal fate. , 2013, Current opinion in cell biology.

[57]  J. Keller,et al.  RNA in Brain Disease: No Longer Just "The Messenger in the Middle" , 2007, Journal of neuropathology and experimental neurology.

[58]  E. Granieri,et al.  Altered miRNA expression in T regulatory cells in course of multiple sclerosis , 2010, Journal of Neuroimmunology.

[59]  Keith W. Jones,et al.  The curious case of miRNAs in circulation: potential diagnostic biomarkers? , 2013, Wiley interdisciplinary reviews. RNA.

[60]  Walter J. Lukiw,et al.  Regulation of Complement Factor H (CFH) by Multiple miRNAs in Alzheimer’s Disease (AD) Brain , 2012, Molecular Neurobiology.

[61]  Hans-Peter Lenhof,et al.  Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls , 2009, PloS one.

[62]  A. Schetter,et al.  Circulating micro‐RNA expression profiles in early stage nonsmall cell lung cancer , 2012, International journal of cancer.

[63]  H. Lassmann,et al.  MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. , 2009, Brain : a journal of neurology.

[64]  Robert L. Tanguay,et al.  Non-coding RNAs--novel targets in neurotoxicity. , 2012, Neurotoxicology.

[65]  D. DeMets,et al.  Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework , 2001, Clinical pharmacology and therapeutics.

[66]  A. Jovičić,et al.  MicroRNA-22 (miR-22) Overexpression Is Neuroprotective via General Anti-Apoptotic Effects and May also Target Specific Huntington’s Disease-Related Mechanisms , 2013, PloS one.

[67]  C. Croce,et al.  Clinical Applications for microRNAs in Cancer , 2013, Clinical pharmacology and therapeutics.

[68]  N. Bresolin,et al.  Role of OLR1 and its regulating hsa-miR369-3p in Alzheimer's disease: genetics and expression analysis. , 2011, Journal of Alzheimer's disease : JAD.

[69]  D. Murphy,et al.  miR-15a and miR-16 regulate serotonin transporter expression in human placental and rat brain raphe cells. , 2013, The international journal of neuropsychopharmacology.

[70]  W. Lukiw,et al.  microRNA (miRNA) speciation in Alzheimer's disease (AD) cerebrospinal fluid (CSF) and extracellular fluid (ECF). , 2012, International journal of biochemistry and molecular biology.

[71]  M. Millan.  MicroRNA in the regulation and expression of serotonergic transmission in the brain and other tissues. , 2011, Current opinion in pharmacology.

[72]  Wei Li,et al.  MicroRNA detection by microarray , 2009, Analytical and bioanalytical chemistry.

[73]  L. Steinman,et al.  Impaired neurosteroid synthesis in multiple sclerosis. , 2011, Brain : a journal of neurology.

[74]  A. Ludolph,et al.  Systemic dysregulation of TDP-43 binding microRNAs in amyotrophic lateral sclerosis , 2013, Acta Neuropathologica Communications.

[75]  G. Lippi,et al.  Epigenetic biomarkers: A new perspective in laboratory diagnostics. , 2012, Clinica chimica acta; international journal of clinical chemistry.

[76]  M. Chopp,et al.  The MicroRNA-17–92 Cluster Enhances Axonal Outgrowth in Embryonic Cortical Neurons , 2013, The Journal of Neuroscience.

[77]  Eduardo Gascon,et al.  Cause or Effect: Misregulation of microRNA Pathways in Neurodegeneration , 2012, Front. Neurosci..

[78]  N. Bresolin,et al.  Expression and genetic analysis of miRNAs involved in CD4+ cell activation in patients with multiple sclerosis , 2011, Neuroscience Letters.

[79]  G. Jicha,et al.  Blood serum miRNA: Non-invasive biomarkers for Alzheimer's disease , 2012, Experimental Neurology.

[80]  A. D. dos Santos,et al.  miR-15a and 16-1 Are Downregulated in CD4+ T Cells of Multiple Sclerosis Relapsing Patients , 2012, The International journal of neuroscience.

[81]  N. Jablonski,et al.  Circulating microRNAs involved in multiple sclerosis , 2012, Molecular Biology Reports.

[82]  Guiliang Tang,et al.  The Expression of MicroRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression through Regulation of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 , 2008, The Journal of Neuroscience.

[83]  Hyman M. Schipper,et al.  MicroRNA Expression in Alzheimer Blood Mononuclear Cells , 2007, Gene regulation and systems biology.

[84]  Mårten Segelmark,et al.  Circulating microRNA expression profiles associated with systemic lupus erythematosus. , 2013, Arthritis and rheumatism.

[85]  R. Katz,et al.  Biomarkers and surrogate markers: An FDA perspective , 2004, NeuroRX.

[86]  Thomas J. Montine,et al.  MicroRNA in Alzheimer’s disease: an exploratory study in brain, cerebrospinal fluid and plasma , 2013, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.