Sammanfattning

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.

Nyckelord

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

Publicerad i

Frontiers in Aging Neuroscience
2019, Volym: 11, artikelnummer: 64
Utgivare: FRONTIERS MEDIA SA

SLU författare

• Härd, Torleif

  • Institutionen för kemi och bioteknologi, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Neurovetenskaper


Publikationens identifierare

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

Permanent länk till denna sida (URI)

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