Alteration of the microRNA network during the progression of Alzheimer's disease

Authors

  • Pierre Lau,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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  • Koen Bossers,

    1. Neurogeneration Group, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
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  • Rekin's Janky,

    1. Laboratory of Computational Biology, Center for Human Genetics and University of Leuven, Leuven, Belgium
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  • Evgenia Salta,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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  • Carlo Sala Frigerio,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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  • Shahar Barbash,

    1. Department of Biological Chemistry, the Silberman Institute of Life Sciences, and the Edmond and Lily Safra Center of Brain Science Interdisciplinary Center for Neural Computation, Jerusalem, Israel
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  • Roy Rothman,

    1. Department of Biological Chemistry, the Silberman Institute of Life Sciences, and the Edmond and Lily Safra Center of Brain Science Interdisciplinary Center for Neural Computation, Jerusalem, Israel
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  • Annerieke S. R. Sierksma,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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  • Amantha Thathiah,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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  • David Greenberg,

    1. Department of Biological Chemistry, the Silberman Institute of Life Sciences, and the Edmond and Lily Safra Center of Brain Science Interdisciplinary Center for Neural Computation, Jerusalem, Israel
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  • Aikaterini S. Papadopoulou,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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  • Tilmann Achsel,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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  • Torik Ayoubi,

    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
    3. Saint James School of Medicine, Kralendijk, Bonaire, Dutch Caribbean, The Netherlands
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  • Hermona Soreq,

    1. Department of Biological Chemistry, the Silberman Institute of Life Sciences, and the Edmond and Lily Safra Center of Brain Science Interdisciplinary Center for Neural Computation, Jerusalem, Israel
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  • Joost Verhaagen,

    1. Neurogeneration Group, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
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  • Dick F. Swaab,

    1. Neuropsychiatric Disorders Group, Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands
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  • Stein Aerts,

    1. Laboratory of Computational Biology, Center for Human Genetics and University of Leuven, Leuven, Belgium
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  • Bart De Strooper

    Corresponding author
    1. VIB Center for the Biology of Disease, Leuven, Belgium
    2. Center for Human Genetics, Leuven Institute for Neurodegenerative Disorders (LIND) University Hospitals Leuven, and University of Leuven, Leuven, Belgium
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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.

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