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Therapeutically effective antibodies against amyloid-β peptide target amyloid-β residues 4−10 and inhibit cytotoxicity and fibrillogenesis

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2002

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McLaurin, JoAnne
Cecal, Roxana
Kierstead, M. E.
Tian, Xiaodan
Phinney, Amie L.
French, J. E.
Lambermon, Mark H. L.
Darabie, Audrey A.
Brown, Mary E.

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Nature Medicine. 2002, 8(11), pp. 1263-1269. ISSN 1078-8956. Available under: doi: 10.1038/nm790

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Immunization of transgenic mouse models of Alzheimer disease using amyloid-β peptide (Aβ) reduces both the Alzheimer disease−like neuropathology and the spatial memory impairments of these mice. However, a therapeutic trial of immunization with Aβ42 in humans was discontinued because a few patients developed significant meningo-encephalitic cellular inflammatory reactions. Here we show that beneficial effects in mice arise from antibodies selectively directed against residues 4−10 of Aβ42, and that these antibodies inhibit both Aβ fibrillogenesis and cytotoxicity without eliciting an inflammatory response. These findings provide the basis for improved immunization antigens as well as attempts to design small-molecule mimics as alternative therapies.

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540 Chemie

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ISO 690MCLAURIN, JoAnne, Roxana CECAL, M. E. KIERSTEAD, Xiaodan TIAN, Amie L. PHINNEY, Marilena MANEA, J. E. FRENCH, Mark H. L. LAMBERMON, Audrey A. DARABIE, Mary E. BROWN, Christopher G JANUS, Muhammad Azhar CHISHTI, Patrick HORNE, David WESTAWAY, Paul FRASER, Howard MOUNT, Michael PRZYBYLSKI, Peter St. GEORGE-HYSLOP, 2002. Therapeutically effective antibodies against amyloid-β peptide target amyloid-β residues 4−10 and inhibit cytotoxicity and fibrillogenesis. In: Nature Medicine. 2002, 8(11), pp. 1263-1269. ISSN 1078-8956. Available under: doi: 10.1038/nm790
BibTex
@article{McLaurin2002-11Thera-17582,
  year={2002},
  doi={10.1038/nm790},
  title={Therapeutically effective antibodies against amyloid-β peptide target amyloid-β residues 4−10 and inhibit cytotoxicity and fibrillogenesis},
  number={11},
  volume={8},
  issn={1078-8956},
  journal={Nature Medicine},
  pages={1263--1269},
  author={McLaurin, JoAnne and Cecal, Roxana and Kierstead, M. E. and Tian, Xiaodan and Phinney, Amie L. and Manea, Marilena and French, J. E. and Lambermon, Mark H. L. and Darabie, Audrey A. and Brown, Mary E. and Janus, Christopher G and Chishti, Muhammad Azhar and Horne, Patrick and Westaway, David and Fraser, Paul and Mount, Howard and Przybylski, Michael and George-Hyslop, Peter St.}
}
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