AUTHOR=Boutajangout Allal , Lindberg Hanna , Awwad Abdulaziz , Paul Arun , Baitalmal Rabaa , Almokyad Ismail , Höidén-Guthenberg Ingmarie , Gunneriusson Elin , Frejd Fredrik Y. , Härd Torleif , Löfblom John , Ståhl Stefan , Wisniewski Thomas 

TITLE=Affibody-Mediated Sequestration of Amyloid β Demonstrates Preventive Efficacy in a Transgenic Alzheimer’s Disease Mouse Model

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=11

YEAR=2019

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00064

DOI=10.3389/fnagi.2019.00064

ISSN=1663-4365

ABSTRACT=<p>Different strategies for treatment and prevention of Alzheimer’s disease (AD) are currently under investigation, including passive immunization with anti-amyloid β (anti-Aβ) monoclonal antibodies (mAbs). Here, we investigate the therapeutic potential of a novel type of Aβ-targeting agent based on an affibody molecule with fundamentally different properties to mAbs. We generated a therapeutic candidate, denoted Z<sub>SYM73</sub>-albumin-binding domain (ABD; 16.8 kDa), by genetic linkage of the dimeric Z<sub>SYM73</sub> affibody for sequestering of monomeric Aβ-peptides and an ABD for extension of its <italic>in vivo</italic> half-life. Amyloid precursor protein (APP)/PS1 transgenic AD mice were administered with Z<sub>SYM73</sub>-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 <italic>in vivo</italic> investigation of a systemically delivered scaffold protein against monomeric Aβ, demonstrating a therapeutic potential for prevention of AD.</p>