The antibody aducanumab reduces Aβ plaques in Alzheimer's disease

  • Nature. 2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323.
Jeff Sevigny  1 ,  Ping Chiao  1 ,  Thierry Bussière  1 ,  Paul H Weinreb  1 ,  Leslie Williams  1 ,  Marcel Maier  2 ,  Robert Dunstan  1 ,  Stephen Salloway  3 ,  Tianle Chen  1 ,  Yan Ling  1 ,  John O'Gorman  1 ,  Fang Qian  1 ,  Mahin Arastu  1 ,  Mingwei Li  1 ,  Sowmya Chollate  1 ,  Melanie S Brennan  1 ,  Omar Quintero-Monzon  1 ,  Robert H Scannevin  1 ,  H Moore Arnold  1 ,  Thomas Engber  1 ,  Kenneth Rhodes  1 ,  James Ferrero  1 ,  Yaming Hang  1 ,  Alvydas Mikulskis  1 ,  Jan Grimm  2 ,  Christoph Hock  2  4 ,  Roger M Nitsch  2  4 ,  Alfred Sandrock  1
Affiliations
  • 1. Biogen, Cambridge, Massachusetts 02142, USA.
  • 2. Neurimmune, Schlieren-Zurich 8952, Switzerland.
  • 3. Butler Hospital, Providence, Rhode Island 02906, USA.
  • 4. Institute for Regenerative Medicine, University of Zurich, Zurich 8952, Switzerland.
PMID: 27582220 DOI: 10.1038/nature19323
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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