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Nature. 2016 Sep 1;537(7618):50-6. doi: 10.1038/nature19323.

The antibody aducanumab reduces Aβ plaques in Alzheimer's disease.

Author information

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.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01677572.

PMID:
27582220
DOI:
10.1038/nature19323
[Indexed for MEDLINE]
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