• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Evidence that brain-reactive autoantibodies contribute to chronic neuronal internalization of exogenous Amyloid-β1-42 and key cell surface proteins during Alzheimer's disease pathogenesis

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Goldwaser, E.L.
    Acharya, N.K.
    Wu, H.
    Date
    2020
    Journal
    Journal of Alzheimer's Disease
    Publisher
    IOS Press
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3233/JAD-190962
    Abstract
    Blood-brain barrier (BBB) permeability is a recognized early feature of Alzheimer’s disease (AD). In the present study, we examined consequences of increased BBB permeability on the development of AD-related pathology by tracking selected leaked plasma components and their interactions with neurons in vivo and in vitro. Histological sections of cortical regions of postmortem AD brains were immunostained to determine the distribution of amyloid-β1-42 (Aβ42), cathepsin D, IgG, GluR2/3, and alpha7 nicotinic acetylcholine receptor (α7nAChR). Results revealed that chronic IgG binding to pyramidal neurons coincided with internalization of Aβ42, IgG, GluR2/3, and α7nAChR as well as lysosomal compartment expansion in these cells in regions of AD pathology. To test possible mechanistic interrelationships of these phenomena, we exposed differentiated SH-SY5Y neuroblastoma cells to exogenous, soluble Aβ42 peptide and serum from AD and control subjects. The rate and extent of Aβ42 internalization in these cells was enhanced by serum containing neuron-binding IgG autoantibodies. This was confirmed by treating cells with individual antibodies specific for α7nAChR, purified IgG from AD or non-AD sera, and sera devoid of IgG, in the presence of 100 nM Aβ42. Initial co-localization of IgG, α7nAChR, and Aβ42 was temporally and spatially linked to early endosomes (Rab11) and later to lysosomes (LAMP-1). Aβ42 internalization was attenuated by treatment with monovalent F(ab) antibody fragments generated from purified IgG from AD serum and then rescued by coupling F(ab) fragments with divalent human anti-Fab. Overall, results suggest that cross-linking of neuron-binding autoantibodies targeting cell surface proteins can accelerate intraneuronal Aβ42 deposition in AD.
    Keyword
    Alzheimer's disease
    autoantibodies
    Amyloid-β1-42
    blood-brain barrier
    brain-reactive autoantibodies
    cerebrovasculature
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85081999452&doi=10.3233%2fJAD-190962&partnerID=40&md5=3ce3f1d25ea9fbcbff1389aa5dce2360; http://hdl.handle.net/10713/12470
    ae974a485f413a2113503eed53cd6c53
    10.3233/JAD-190962
    Scopus Count
    Collections
    UMB Open Access Articles

    entitlement

    Related articles

    • Brain-reactive autoantibodies prevalent in human sera increase intraneuronal amyloid-β(1-42) deposition.
    • Authors: Nagele RG, Clifford PM, Siu G, Levin EC, Acharya NK, Han M, Kosciuk MC, Venkataraman V, Zavareh S, Zarrabi S, Kinsler K, Thaker NG, Nagele EP, Dash J, Wang HY, Levitas A
    • Issue date: 2011
    • Targeting the alpha 7 nicotinic acetylcholine receptor to reduce amyloid accumulation in Alzheimer's disease pyramidal neurons.
    • Authors: D'Andrea MR, Nagele RG
    • Issue date: 2006
    • Mitogen-activated protein kinase signaling pathways are involved in regulating α7 nicotinic acetylcholine receptor-mediated amyloid-β uptake in SH-SY5Y cells.
    • Authors: Yang WN, Ma KG, Chen XL, Shi LL, Bu G, Hu XD, Han H, Liu Y, Qian YH
    • Issue date: 2014 Oct 10
    • Increased Aβ(42)-α7-like nicotinic acetylcholine receptor complex level in lymphocytes is associated with apolipoprotein E4-driven Alzheimer's disease pathogenesis.
    • Authors: Wang HY, Trocmé-Thibierge C, Stucky A, Shah SM, Kvasic J, Khan A, Morain P, Guignot I, Bouguen E, Deschet K, Pueyo M, Mocaer E, Ousset PJ, Vellas B, Kiyasova V
    • Issue date: 2017 Jul 27
    • Mitogen-activated protein kinase signaling pathways promote low-density lipoprotein receptor-related protein 1-mediated internalization of beta-amyloid protein in primary cortical neurons.
    • Authors: Yang WN, Ma KG, Qian YH, Zhang JS, Feng GF, Shi LL, Zhang ZC, Liu ZH
    • Issue date: 2015 Jul
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.