title: miR-132 loss de-represses ITPKB and aggravates amyloid and TAU pathology in Alzheimer's brain.
abstract: microRNA-132 (miR-132) is involved in prosurvival, anti-inflammatory and memory-promoting functions in the nervous system and has been found consistently downregulated in Alzheimer's disease (AD). Whether and how miR-132 deficiency impacts AD pathology remains, however, unaddressed. We show here that miR-132 loss exacerbates both amyloid and TAU pathology via inositol 1,4,5-trisphosphate 3-kinase B (ITPKB) upregulation in an AD mouse model. This leads to increased ERK1/2 and BACE1 activity and elevated TAU phosphorylation. We confirm downregulation of miR-132 and upregulation of ITPKB in three distinct human AD patient cohorts, indicating the pathological relevance of this pathway in AD.
authors.affiliation: VIB Center for the Biology of Disease, Leuven, Belgium Center for Human Genetics, Universitaire ziekenhuizen and LIND, KU, Leuven, Belgium.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Salta
authors.affiliation: VIB Center for the Biology of Disease, Leuven, Belgium Center for Human Genetics, Universitaire ziekenhuizen and LIND, KU, Leuven, Belgium.
authors.forename: Annerieke
authors.initials: A
authors.lastname: Sierksma
authors.affiliation: VIB Center for the Biology of Disease, Leuven, Belgium Center for Human Genetics, Universitaire ziekenhuizen and LIND, KU, Leuven, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Vanden Eynden
authors.affiliation: VIB Center for the Biology of Disease, Leuven, Belgium Center for Human Genetics, Universitaire ziekenhuizen and LIND, KU, Leuven, Belgium Institute of Neurology, University College London, London, UK bart.destrooper@cme.vib-kuleuven.be.
authors.forename: Bart
authors.identifier: 0000-0001-5455-5819
authors.initials: B
authors.lastname: De Strooper
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000682:Amyloid; C547077:MIRN132 microRNA, human; C546976:MIRN132 microRNA, mouse; C558298:Mapt protein, mouse; D035683:MicroRNAs; D016875:tau Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Alzheimer's; ITPKB; TAU; amyloid; microRNA‐132