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Research article - Peer-reviewed, 2019

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


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.


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

Authors' information

Boutajangout, Allal
New York University
Lindberg, Hanna
Royal Institute of Technology
Awwad, Abdulaziz
King Abdulaziz University
Paul, Arun
New York University
Baitalmal, Rabaa
New York University
Almokyad, Ismail
New York University
Hoiden-Guthenberg, Ingmarie
Affibody AB
Gunneriusson, Elin
Affibody AB
Frejd, Fredrik Y.
Affibody AB
Swedish University of Agricultural Sciences, The Department of Chemistry and Biotechnology
Lofblom, John
Royal Institute of Technology
Stahl, Stefan
Royal Institute of Technology
Wisniewski, Thomas
New York University

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