An in vitro paradigm to assess potential anti-Aβ antibodies for Alzheimer’s disease
Ming Jin,
Brian O’Nuallain,
Wei Hong,
Justin Boyd,
Valentina N. Lagomarsino,
Tiernan T. O’Malley,
Wen Liu,
Charles R. Vanderburg,
Matthew P. Frosch,
Tracy Young-Pearse,
Dennis J. Selkoe () and
Dominic M. Walsh ()
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Ming Jin: Brigham and Women’s Hospital and Harvard Medical School
Brian O’Nuallain: Brigham and Women’s Hospital and Harvard Medical School
Wei Hong: Brigham and Women’s Hospital and Harvard Medical School
Justin Boyd: Brigham and Women’s Hospital and Harvard Medical School
Valentina N. Lagomarsino: Brigham and Women’s Hospital and Harvard Medical School
Tiernan T. O’Malley: Brigham and Women’s Hospital and Harvard Medical School
Wen Liu: Brigham and Women’s Hospital and Harvard Medical School
Charles R. Vanderburg: Massachusetts General Hospital and Harvard Medical School
Matthew P. Frosch: Massachusetts General Hospital and Harvard Medical School
Tracy Young-Pearse: Brigham and Women’s Hospital and Harvard Medical School
Dennis J. Selkoe: Brigham and Women’s Hospital and Harvard Medical School
Dominic M. Walsh: Brigham and Women’s Hospital and Harvard Medical School
Nature Communications, 2018, vol. 9, issue 1, 1-13
Abstract:
Abstract Although the amyloid β-protein (Aβ) is believed to play an initiating role in Alzheimer’s disease (AD), the molecular characteristics of the key pathogenic Aβ forms are not well understood. As a result, it has proved difficult to identify optimal agents that target disease-relevant forms of Aβ. Here, we combined the use of Aβ-rich aqueous extracts of brain samples from AD patients as a source of human Aβ and live-cell imaging of iPSC-derived human neurons to develop a bioassay capable of quantifying the relative protective effects of multiple anti-Aβ antibodies. We report the characterization of 1C22, an aggregate-preferring murine anti-Aβ antibody, which better protects against forms of Aβ oligomers that are toxic to neurites than do the murine precursors of the clinical immunotherapeutics, bapineuzumab and solanezumab. These results suggest further examination of 1C22 is warranted, and that this bioassay maybe useful as a primary screen to identify yet more potent anti-Aβ therapeutics.
Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05068-w
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DOI: 10.1038/s41467-018-05068-w
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