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Research article2019Peer reviewedOpen access

Affibody-Mediated Sequestration of Amyloid beta Demonstrates Preventive Efficacy in a Transgenic Alzheimer's Disease Mouse Model

Boutajangout, Allal; Lindberg, Hanna; Awwad, Abdulaziz; Paul, Arun; Baitalmal, Rabaa; Almokyad, Ismail; Hoiden-Guthenberg, Ingmarie; Gunneriusson, Elin; Frejd, Fredrik Y.; Hard, Torleif; Lofblom, John; Stahl, Stefan; Wisniewski, Thomas

Abstract

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.

Keywords

Alzheimer's disease; affibody molecule; amyloid beta (A beta); behavior; histology; immunotherapy; transgenic mice

Published in

Frontiers in Aging Neuroscience
2019, volume: 11, article number: 64
Publisher: FRONTIERS MEDIA SA

SLU Authors

  • Härd, Torleif

    • The Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences

UKÄ Subject classification

Neurosciences

Publication identifier

  • DOI: https://doi.org/10.3389/fnagi.2019.00064

Permanent link to this page (URI)

https://res.slu.se/id/publ/99569