LRP/LR specific antibody IgG1-iS18 impedes neurodegeneration in Alzheimer's disease mice

Eloise Ferreira; Monique J. Bignoux; Tyrone C. Otgaar; Nicolas Tagliatti; Katarina Jovanovic; Boitelo T. Letsolo; Stefan F.T. Weiss

doi:10.18632/oncotarget.25473

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Research Papers:

LRP/LR specific antibody IgG1-iS18 impedes neurodegeneration in Alzheimer's disease mice

Eloise Ferreira, Monique J. Bignoux, Tyrone C. Otgaar, Nicolas Tagliatti, Katarina Jovanovic, Boitelo T. Letsolo and Stefan F.T. Weiss _

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Oncotarget. 2018; 9:27059-27073. https://doi.org/10.18632/oncotarget.25473

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Abstract

Eloise Ferreira1, Monique J. Bignoux1, Tyrone C. Otgaar1, Nicolas Tagliatti1, Katarina Jovanovic1,2, Boitelo T. Letsolo1 and Stefan F.T. Weiss1

1School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, Republic of South Africa

2Present address: UCL Institute of Ophthalmology, London, UK

Correspondence to:

Stefan F.T. Weiss, email: [email protected]

Keywords: Alzheimer’s disease; amyloid beta; LRP-LR; therapeutic antibody; transgenic mice

Received: September 12, 2017 Accepted: May 08, 2018 Published: June 05, 2018

ABSTRACT

Alzheimer’s disease (AD) is a neurodegenerative disease caused by accumulation of amyloid beta (Aβ) plaque and neurofibrillary tangle formation. We have shown in vitro, that knock-down and blockade of the 37 kDa/67 kDa Laminin Receptor (LRP/LR) resulted in reduced Aβ induced cytotoxicity and Aβ accumulation. In order to test the effect of blocking LRP/LR on Aβ formation and AD associated symptoms, AD transgenic mice received the anti-LRP/LR specific antibody, IgG1-iS18 through intranasal administration. We show that this treatment resulted in an improvement in memory, and decreased Aβ plaque formation. Moreover, a significant decrease in Aβ₄₂ protein expression with a concomitant increase in amyloid precursor protein (APP) and telomerase reverse transcriptase (mTERT) levels was observed. These data recommend IgG1-iS18 as a potentially powerful therapeutic antibody for AD treatment.

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Research Papers:

LRP/LR specific antibody IgG1-iS18 impedes neurodegeneration in Alzheimer's disease mice

Abstract