Amyloid β protein immunotherapy neutralizes Aβ oligomers that disrupt synaptic plasticity in vivo
| العنوان: | Amyloid β protein immunotherapy neutralizes Aβ oligomers that disrupt synaptic plasticity in vivo |
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| المؤلفون: | Vicki Betts, Dennis J. Selkoe, Michael J. Rowan, Dominic M. Walsh, Igor Klyubin, William K. Cullen, Cynthia A. Lemere, Liying Jiang, Ganesh M. Shankar, Roger Anwyl, Edward T. Spooner |
| المصدر: | Nature Medicine. 11:556-561 |
| بيانات النشر: | Springer Science and Business Media LLC, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | medicine.drug_class, Long-Term Potentiation, Hippocampus, Enzyme-Linked Immunosorbent Assay, CHO Cells, Pharmacology, Active immunization, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Cricetulus, Alzheimer Disease, Neutralization Tests, In vivo, Cricetinae, medicine, Animals, Immunoprecipitation, Amyloid beta-Peptides, Neuronal Plasticity, biology, Antibodies, Monoclonal, Long-term potentiation, General Medicine, medicine.disease, Immunohistochemistry, Peptide Fragments, Rats, Electrophysiology, Biochemistry, Synapses, Synaptic plasticity, Chromatography, Gel, biology.protein, Immunization, Antibody, Alzheimer's disease |
| الوصف: | One of the most clinically advanced forms of experimental disease-modifying treatment for Alzheimer disease is immunization against the amyloid β protein (Aβ)1,2,3,4,5,6,7, but how this may prevent cognitive impairment is unclear8,9,10,11,12,13. We hypothesized that antibodies to Aβ could exert a beneficial action by directly neutralizing potentially synaptotoxic soluble Aβ species14,15,16 in the brain. Intracerebroventricular injection of naturally secreted human Aβ inhibited long-term potentiation (LTP), a correlate of learning and memory17, in rat hippocampus in vivo but a monoclonal antibody to Aβ completely prevented the inhibition of LTP when injected after Aβ. Size fractionation showed that Aβ oligomers, not monomers or fibrils, were responsible for inhibiting LTP, and an Aβ antibody again prevented such inhibition. Active immunization against Aβ was partially effective, and the effects correlated positively with levels of antibodies to Aβ oligomers. The ability of exogenous and endogenous antibodies to rapidly neutralize soluble Aβ oligomers that disrupt synaptic plasticity in vivo suggests that treatment with such antibodies might show reversible cognitive deficits in early Alzheimer disease. |
| تدمد: | 1546-170X 1078-8956 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea76dee0c0f1267acef1a3a4a5571e4a https://doi.org/10.1038/nm1234 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....ea76dee0c0f1267acef1a3a4a5571e4a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1546170X 10788956 |
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