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  • 1.
    Boutajangout, Allal
    et al.
    NYU, Ctr Cognit Neurol, Langone Hlth, New York, NY 10016 USA.;NYU, Dept Neurol, Langone Hlth, New York, NY 10016 USA.;NYU, Dept Psychiat, Langone Hlth, 550 1St Ave, New York, NY 10016 USA.;NYU, Langone Med Ctr, Dept Physiol & Neurosci, New York, NY USA..
    Lindberg, Hanna
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Awwad, Abdulaziz
    King Abdulaziz Univ, Sch Med, Jeddah, Saudi Arabia..
    Paul, Arun
    NYU, Ctr Cognit Neurol, Langone Hlth, New York, NY 10016 USA.;NYU, Dept Neurol, Langone Hlth, New York, NY 10016 USA..
    Baitalmal, Rabaa
    NYU, Ctr Cognit Neurol, Langone Hlth, New York, NY 10016 USA.;NYU, Dept Neurol, Langone Hlth, New York, NY 10016 USA..
    Almokyad, Ismail
    NYU, Ctr Cognit Neurol, Langone Hlth, New York, NY 10016 USA.;NYU, Dept Neurol, Langone Hlth, New York, NY 10016 USA..
    Hoiden-Guthenberg, Ingmarie
    Affibody AB, Solna, Sweden..
    Gunneriusson, Elin
    Affibody AB, Solna, Sweden..
    Frejd, Fredrik Y.
    Affibody AB, Solna, Sweden..
    Hard, Torleif
    Swedish Univ Agr Sci SLU, Dept Chem & Biotechnol, Uppsala, Sweden..
    Löfblom, John
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Ståhl, Stefan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Wisniewski, Thomas
    NYU, Ctr Cognit Neurol, Langone Hlth, New York, NY 10016 USA.;NYU, Dept Neurol, Langone Hlth, New York, NY 10016 USA.;NYU, Dept Psychiat, Langone Hlth, 550 1St Ave, New York, NY 10016 USA.;NYU, Sch Med, Dept Pathol, New York, NY 10016 USA..
    Affibody-Mediated Sequestration of Amyloid beta Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model2019In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 11, article id 64Article in journal (Refereed)
    Abstract [en]

    Different strategies for treatment and prevention of Alzheimer's disease (AD) are currently under investigation, including passive immunization with anti-amyloid beta (anti-A beta) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of A beta-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted Z(SYM73)-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric Z(SYM73) affibody for sequestering of monomeric A beta-peptides and an ABD for extension of its in vivo half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with Z(SYM73)-ABD, followed by behavioral examination and immunohistochemistry. Results demonstrated rescued cognitive functions and significantly lower amyloid burden in the treated animals compared to controls. No toxicological symptoms or immunology-related side-effects were observed. To our knowledge, this is the first reported in vivo investigation of a systemically delivered scaffold protein against monomeric A beta, demonstrating a therapeutic potential for prevention of AD.

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