title: Circulating miRNAs as potential biomarkers in Alzheimer's disease.
abstract: Several micro(mi)RNA are deregulated in brain, cerebrospinal fluid (CSF), and serum/plasma from patients with Alzheimer's disease (AD). The aim of the study was to profile circulating miRNAs in serum as non-invasive biomarkers for AD, correlating them with those identified in CSF, the biological fluid which better reflects biochemical changes occurring during pathological processes in the brain and may provide a robust indicator of AD-related disease pathogenesis thanks to the evidence of low amyloid and high levels of tau and hyperphosphorylated tau. Using a two-step analysis (array and validation through real-time PCR), a down-regulation (mean fold change ± SEM) of miR-125b (0.415 ± 0.11 versus 1.381 ± 0.36, p = 0.009), miR-23a (0.111 ± 0.03 versus 0.732 ± 0.14, p < 0.001), and miR-26b (0.414 ± 0.11 versus 1.353 ± 0.39, p < 0.01), out of 84 tested, was shown in serum from 22 AD patients compared with 18 non-inflammatory and 8 inflammatory neurological controls (NINDCs and INDCs) and 10 patients with frontotemporal dementia. Significant down-regulation of miR-125b and miR-26b was also confirmed in CSF from AD patients versus NINDCs (miR-125b: 0.089 ± 0.03 versus 0.230 ± 0.08, p < 0.001; miR-26b: 0.217 ± 0.06 versus 1.255 ± 0.29, p < 0.001, mean fold change ± SEM, respectively), whereas data were not replicated for miR-23a. In serum, miR-125b had an AUC of 0.82 to distinguish AD from NINDCs (95% CI: 0.65-0.98, p = 0.005). In conclusion, we demonstrated that cell-free miR-125b serum levels are decreased in serum from patients with AD as compared with NINDC and distinguish between AD and NINDCs with an accuracy of 82%.
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Serpente
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ghezzi
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Sara M G
authors.initials: SM
authors.lastname: Cioffi
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Arighi
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fumagalli
authors.affiliation: Neurology Unit, Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000097:blood / Q000134:cerebrospinal fluid; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D057180:Frontotemporal Dementia / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000097:blood / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D035683:MicroRNAs; D010446:Peptide Fragments; D016875:tau Proteins; C054369:MAPT protein, human; C531888:MIRN125 microRNA, human; C552430:MIRN23a microRNA, human; C528163:MIRN26 microRNA, human; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer's disease; biomarker; miRNA; serum