Title |
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
|
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Published in |
Nature, August 2016
|
DOI | 10.1038/nature19323 |
Pubmed ID | |
Authors |
Jeff Sevigny, Ping Chiao, Thierry Bussière, Paul H. Weinreb, Leslie Williams, Marcel Maier, Robert Dunstan, Stephen Salloway, Tianle Chen, Yan Ling, John O’Gorman, Fang Qian, Mahin Arastu, Mingwei Li, Sowmya Chollate, Melanie S. Brennan, Omar Quintero-Monzon, Robert H. Scannevin, H. Moore Arnold, Thomas Engber, Kenneth Rhodes, James Ferrero, Yaming Hang, Alvydas Mikulskis, Jan Grimm, Christoph Hock, Roger M. Nitsch, Alfred Sandrock |
Abstract |
Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its neurotoxicity has so far been unsuccessful. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. In patients with prodromal or mild AD, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner. This is accompanied by a slowing of clinical decline measured by Clinical Dementia Rating-Sum of Boxes and Mini Mental State Examination scores. The main safety and tolerability findings are amyloid-related imaging abnormalities. These results justify further development of aducanumab for the treatment of AD. Should the slowing of clinical decline be confirmed in ongoing phase 3 clinical trials, it would provide compelling support for the amyloid hypothesis. |
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Japan | 135 | 12% |
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Spain | 41 | 4% |
Australia | 29 | 3% |
Canada | 24 | 2% |
France | 15 | 1% |
India | 10 | <1% |
Germany | 9 | <1% |
Other | 137 | 12% |
Unknown | 494 | 44% |
Demographic breakdown
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Members of the public | 882 | 78% |
Scientists | 176 | 16% |
Practitioners (doctors, other healthcare professionals) | 56 | 5% |
Science communicators (journalists, bloggers, editors) | 20 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 13 | <1% |
United Kingdom | 11 | <1% |
Spain | 7 | <1% |
Germany | 5 | <1% |
Japan | 4 | <1% |
France | 3 | <1% |
Brazil | 3 | <1% |
Egypt | 2 | <1% |
Macao | 1 | <1% |
Other | 11 | <1% |
Unknown | 3284 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 516 | 15% |
Researcher | 504 | 15% |
Student > Bachelor | 503 | 15% |
Student > Master | 347 | 10% |
Other | 166 | 5% |
Other | 501 | 15% |
Unknown | 807 | 24% |
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Medicine and Dentistry | 377 | 11% |
Agricultural and Biological Sciences | 376 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 177 | 5% |
Other | 556 | 17% |
Unknown | 926 | 28% |