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Immunomodulation of AβPP processing alleviates amyloid-β-related pathology in Alzheimer's disease transgenic mice.
J Alzheimers Dis. 2010; 22(2):469-82.JA

Abstract

Among the different paradigms aimed at interfering with amyloid-β (Aβ)-related pathology, the attenuation of amyloid-β protein precursor (AβPP) processing to limit Aβ levels seems to be a promising one. Along with the development of BACE1 inhibitors, and the generation of its knock-out mice, accumulating data raise concerns regarding a total inhibition of the enzyme as it shares the processing of other substrates. We described a novel approach to interfere with the specific interaction between AβPP and BACE1 using monoclonal antibodies directed to the β-secretase cleavage site upon the substrate, AβPP. Such antibodies limit AβPP cleavage in a cellular model of Alzheimer's disease (AD) and avoid the total inhibition of BACE1. Here, we demonstrate the ability of AβPP β-site antibodies to interfere with Aβ production in vivo. Systemic antibody treatment diminished Aβ plaques, membrane-associated oligomers, and intracellular Aβ accumulation, all of which have been implicated in cellular death and synaptic loss, suggesting that this approach may be an applicable strategy for AD treatment.

Authors+Show Affiliations

Department of Molecular Microbiology & Biotechnology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20847413

Citation

Arbel-Ornath, Michal, et al. "Immunomodulation of AβPP Processing Alleviates Amyloid-β-related Pathology in Alzheimer's Disease Transgenic Mice." Journal of Alzheimer's Disease : JAD, vol. 22, no. 2, 2010, pp. 469-82.
Arbel-Ornath M, Becker M, Rabinovich-Toidman P, et al. Immunomodulation of AβPP processing alleviates amyloid-β-related pathology in Alzheimer's disease transgenic mice. J Alzheimers Dis. 2010;22(2):469-82.
Arbel-Ornath, M., Becker, M., Rabinovich-Toidman, P., Gartner, M., & Solomon, B. (2010). Immunomodulation of AβPP processing alleviates amyloid-β-related pathology in Alzheimer's disease transgenic mice. Journal of Alzheimer's Disease : JAD, 22(2), 469-82. https://doi.org/10.3233/JAD-2010-100753
Arbel-Ornath M, et al. Immunomodulation of AβPP Processing Alleviates Amyloid-β-related Pathology in Alzheimer's Disease Transgenic Mice. J Alzheimers Dis. 2010;22(2):469-82. PubMed PMID: 20847413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunomodulation of AβPP processing alleviates amyloid-β-related pathology in Alzheimer's disease transgenic mice. AU - Arbel-Ornath,Michal, AU - Becker,Maria, AU - Rabinovich-Toidman,Polina, AU - Gartner,Myra, AU - Solomon,Beka, PY - 2010/9/18/entrez PY - 2010/9/18/pubmed PY - 2011/3/10/medline SP - 469 EP - 82 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 22 IS - 2 N2 - Among the different paradigms aimed at interfering with amyloid-β (Aβ)-related pathology, the attenuation of amyloid-β protein precursor (AβPP) processing to limit Aβ levels seems to be a promising one. Along with the development of BACE1 inhibitors, and the generation of its knock-out mice, accumulating data raise concerns regarding a total inhibition of the enzyme as it shares the processing of other substrates. We described a novel approach to interfere with the specific interaction between AβPP and BACE1 using monoclonal antibodies directed to the β-secretase cleavage site upon the substrate, AβPP. Such antibodies limit AβPP cleavage in a cellular model of Alzheimer's disease (AD) and avoid the total inhibition of BACE1. Here, we demonstrate the ability of AβPP β-site antibodies to interfere with Aβ production in vivo. Systemic antibody treatment diminished Aβ plaques, membrane-associated oligomers, and intracellular Aβ accumulation, all of which have been implicated in cellular death and synaptic loss, suggesting that this approach may be an applicable strategy for AD treatment. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/20847413/Immunomodulation_of_AβPP_processing_alleviates_amyloid_β_related_pathology_in_Alzheimer's_disease_transgenic_mice_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2010-100753 DB - PRIME DP - Unbound Medicine ER -