期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 53, 期 4, 页码 1485-1497出版社
IOS PRESS
DOI: 10.3233/JAD-150882
关键词
15B3 antibody; Alzheimer's disease; amyloid beta-protein (1-42); oligomers; prion protein; prions; oligomers
资金
- NIH Office of Research Infrastructure Program [P40 OD010440]
- Telethon Italy [TDRC00508TU]
- Italian Ministry of Health [GR-2010-2312769]
15B3 is a monoclonal IgM antibody that selectively detects pathological aggregates of the prion protein (PrP). We report the unexpected finding that 15B3 also recognizes oligomeric but not monomeric forms of amyloid-beta (A beta)(42), an aggregating peptide implicated in the pathogenesis of Alzheimer's disease (AD). The 15B3 antibody: i) inhibits the binding of synthetic A beta(42) oligomers to recombinant PrP and neuronal membranes; ii) prevents oligomer-induced membrane depolarization; iii) antagonizes the inhibitory effects of oligomers on the physiological pharyngeal contractions of the nematode Caenorhabditis elegans; and iv) counteracts the memory deficits induced by intracerebroventricular injection of A beta(42) oligomers in mice. Thus this antibody binds to pathologically relevant forms of A beta, and offers a potential research, diagnostic, and therapeutic tool for AD.
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