TITLE

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

AUTHOR(S)
McLaurin, J.; Cecal, R.; Kierstead, M.E.; Tian, X.; Phinney, A.L.; Manea, M.; French, J.E.; Lambermon, M.H.L.; Darabie, A.A.; Brown, M.E.; Janus, C.; Chishti, M.A.; Horne, P.; Westaway, D.; Fraser, P.E.; Mount, H.T.J.; Przybylski, M.; St George-Hyslop, P.
PUB. DATE
November 2002
SOURCE
Nature Medicine;Nov2002, Vol. 8 Issue 11, p1263
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 Aβ[sub 42] 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 Aβ[sub 42], 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.
ACCESSION #
7746107

 

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