title: Bridging integrator 1 (BIN1) protein expression increases in the Alzheimer's disease brain and correlates with neurofibrillary tangle pathology.
abstract: Recent genome wide association studies have implicated bridging integrator 1 (BIN1) as a late-onset Alzheimer's disease (AD) susceptibility gene. There are at least 15 different known isoforms of BIN1, with many being expressed in the brain including the longest isoform (iso1), which is brain-specific and localizes to axon initial segments and nodes of Ranvier. It is currently unknown what role BIN1 plays in AD. We analyzed BIN1 protein expression from a large number (n = 71) of AD cases and controls from five different brain regions (hippocampus, inferior parietal cortex, inferior temporal cortex, frontal cortex (BA9), and superior and middle temporal gyri). We found that the amount of the largest isoform of BIN1 was significantly reduced in the AD brain compared to age-matched controls, and smaller BIN1 isoforms were significantly increased. Further, BIN1 was significantly correlated with the amount of neurofibrillary tangle (NFT) pathology but not with either diffuse or neuritic plaques, or with the amount of amyloid-β peptide. BIN1 is known to be abnormally expressed in another human disease, myotonic dystrophy, which also features prominent NFT pathology. These data suggest that BIN1 is likely involved in AD as a modulator of NFT pathology, and that this role may extend to other human diseases that feature tau pathology.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Holler
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, USA.
authors.forename: Paulina R
authors.initials: PR
authors.lastname: Davis
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Platt
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Webb
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA University of Kentucky Center for Muscle Biology, University of Kentucky, Lexington, KY, USA.
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; C101410:BIN1 protein, human; C054369:MAPT protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D016875:tau Proteins
keywords: Alzheimer's disease; ZNF9; amyloid-β peptide; cellular nucleic acid binding protein; myotonic dystrophy; tau