The antibody aducanumab reduces Aβ plaques in Alzheimer's disease
- PMID:27582220
- DOI: 10.1038/nature19323
The antibody aducanumab reduces Aβ plaques in Alzheimer's disease
Update in
- Addendum: The antibody aducanumab reduces Aβ plaques in Alzheimer's disease.Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A.Sevigny J, et al.Nature. 2017 Jun 21;546(7659):564. doi: 10.1038/nature22809.Nature. 2017.PMID:28640269
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.govNCT01677572.
Comment in
- Alzheimer's disease: Attack on amyloid-β protein.Reiman EM.Reiman EM.Nature. 2016 Sep 1;537(7618):36-7. doi: 10.1038/537036a.Nature. 2016.PMID:27582214No abstract available.
- Aducanumab reduces Aβ plaques in Alzheimer's disease.Vaillancourt DE.Vaillancourt DE.Mov Disord. 2016 Nov;31(11):1631. doi: 10.1002/mds.26833. Epub 2016 Oct 14.Mov Disord. 2016.PMID:27739124No abstract available.
- Amyloid Cascade into Clarity.Weitz TM, Town T.Weitz TM, et al.Immunity. 2016 Oct 18;45(4):717-718. doi: 10.1016/j.immuni.2016.10.006.Immunity. 2016.PMID:27760336
- How to defeat dementia.Dolgin E.Dolgin E.Nature. 2016 Nov 10;539(7628):156-158. doi: 10.1038/539156a.Nature. 2016.PMID:27830826No abstract available.