title: Myelin basic protein associates with AβPP, Aβ1-42, and amyloid plaques in cortex of Alzheimer's disease brain.
abstract: The goal of this study was to show that myelin and axons in cortical gray matter are damaged in Alzheimer's disease (AD) brain. Superior temporal gyrus gray matter of AD patients (9 male, 14 female) was compared to cognitively normal controls (8 male, 7 female). Myelin basic protein (MBP) and a degraded myelin basic protein complex (dMBP) were quantified by Western blot. Brain sections were immunostained for MBP, dMBP, axonal neurofilament protein (NF), autophagy marker microtubule-associated proteins 1A/B light chain 3B precursor (LC3B), amyloid-β protein precursor (AβPP), and amyloid markers amyloid β1-42 (Aβ1-42) and FSB. Co-immunoprecipitation and mass spectroscopy evaluated interaction of AβPP/Aβ1-42 with MBP/dMBP. Evidence of axonal injury in AD cortex included appearance of AβPP in NF stained axons, and NF at margins of amyloid plaques. Evidence of myelin injury in AD cortex included (1) increased dMBP in AD gray matter compared to control (p < 0.001); (2) dMBP in AD neurons; and (3) increased LC3B that co-localized with MBP. Evidence of interaction of AβPP/Aβ1-42 with myelin or axonal components included (1) greater binding of dMBP with AβPP in AD brain; (2) MBP at the margins of amyloid plaques; (3) dMBP co-localized with Aβ1-42 in the core of amyloid plaques in AD brains; and (4) interactions between Aβ1-42 and MBP/dMBP by co-immunoprecipitation and mass spectrometry. We conclude that damaged axons may be a source of AβPP. dMBP, MBP, and NF associate with amyloid plaques and dMBP associates with AβPP and Aβ1-42. These molecules could be involved in formation of amyloid plaques.
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors.forename: Glen C
authors.initials: GC
authors.lastname: Jickling
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Ander
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors.forename: Boryana
authors.initials: B
authors.lastname: Stamova
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors.forename: DaZhi
authors.initials: D
authors.lastname: Liu
authors.affiliation: Alzheimer's Disease Center, University of California at Davis, Sacramento, CA, USA Department of Pathology, University of California at Davis, Sacramento, CA, USA.
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Kao
authors.affiliation: Alzheimer's Disease Center, University of California at Davis, Sacramento, CA, USA Department of Pathology, University of California at Davis, Sacramento, CA, USA.
authors.forename: Mariko A
authors.initials: MA
authors.lastname: Zelin
authors.affiliation: Alzheimer's Disease Center, University of California at Davis, Sacramento, CA, USA Department of Pathology, University of California at Davis, Sacramento, CA, USA.
authors.forename: Lee-Way
authors.initials: LW
authors.lastname: Jin
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA Alzheimer's Disease Center, University of California at Davis, Sacramento, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Sharp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism*; D016900:Neurofilament Proteins; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000473:pathology*; D053719:Tandem Mass Spectrometry
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C061195:neurofilament protein M
keywords: Alzheimer's disease; amyloid-β; amyloid-β protein precursor; autophagy; axon damage; degraded myelin basic protein; myelin basic protein