title: Alteration of the microRNA network during the progression of Alzheimer's disease.
abstract: An overview of miRNAs altered in Alzheimer's disease (AD) was established by profiling the hippocampus of a cohort of 41 late-onset AD (LOAD) patients and 23 controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the prefrontal cortex of a second independent cohort of 49 patients grouped by Braak stages revealed 41 deregulated miRNAs. We focused on miR-132-3p which is strongly altered in both brain areas. Downregulation of this miRNA occurs already at Braak stages III and IV, before loss of neuron-specific miRNAs. Next-generation sequencing confirmed a strong decrease of miR-132-3p and of three family-related miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR-132-3p in AD brain appears to occur mainly in neurons displaying Tau hyper-phosphorylation. We provide evidence that miR-132-3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this pathway.
authors.affiliation: VIB Center for the Biology of Disease, Leuven, Belgium; Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, O&N4, Herestraat, Leuven, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lau
authors.forename: Koen
authors.initials: K
authors.lastname: Bossers
authors.forename: Rekin's
authors.initials: R
authors.lastname: Janky
authors.forename: Evgenia
authors.initials: E
authors.lastname: Salta
authors.forename: Carlo Sala
authors.initials: CS
authors.lastname: Frigerio
authors.forename: Shahar
authors.initials: S
authors.lastname: Barbash
authors.forename: Roy
authors.initials: R
authors.lastname: Rothman
authors.forename: Annerieke S R
authors.initials: AS
authors.lastname: Sierksma
authors.forename: Amantha
authors.initials: A
authors.lastname: Thathiah
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.forename: Aikaterini S
authors.initials: AS
authors.lastname: Papadopoulou
authors.forename: Tilmann
authors.initials: T
authors.lastname: Achsel
authors.forename: Torik
authors.initials: T
authors.lastname: Ayoubi
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.forename: Stein
authors.initials: S
authors.lastname: Aerts
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019540:Area Under Curve; D001921:Brain / Q000378:metabolism; D002886:Chromosomes, Human, Pair 17; D016000:Cluster Analysis; D015331:Cohort Studies; D018450:Disease Progression; D015536:Down-Regulation; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D012372:ROC Curve; D012720:Severity of Illness Index; D016875:tau Proteins / Q000378:metabolism
chemical_list: C547077:MIRN132 microRNA, human; D035683:MicroRNAs; D016875:tau Proteins
keywords: Alzheimer's disease; hippocampus; miR-132-3p; microRNA; prefrontal cortex