title: The antibody aducanumab reduces Aβ plaques in Alzheimer's disease.
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.
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Jeff
authors: J
authors: Sevigny
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Ping
authors: P
authors: Chiao
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Thierry
authors: T
authors: Bussière
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Paul H
authors: PH
authors: Weinreb
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Leslie
authors: L
authors: Williams
authors: Neurimmune, Schlieren-Zurich 8952, Switzerland.
authors: Marcel
authors: M
authors: Maier
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Robert
authors: R
authors: Dunstan
authors: Butler Hospital, Providence, Rhode Island 02906, USA.
authors: Stephen
authors: S
authors: Salloway
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Tianle
authors: T
authors: Chen
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Yan
authors: Y
authors: Ling
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: John
authors: J
authors: O'Gorman
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Fang
authors: F
authors: Qian
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Mahin
authors: M
authors: Arastu
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Mingwei
authors: M
authors: Li
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Sowmya
authors: S
authors: Chollate
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Melanie S
authors: MS
authors: Brennan
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Omar
authors: O
authors: Quintero-Monzon
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Robert H
authors: RH
authors: Scannevin
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: H Moore
authors: HM
authors: Arnold
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Thomas
authors: T
authors: Engber
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Kenneth
authors: K
authors: Rhodes
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: James
authors: J
authors: Ferrero
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Yaming
authors: Y
authors: Hang
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Alvydas
authors: A
authors: Mikulskis
authors: Neurimmune, Schlieren-Zurich 8952, Switzerland.
authors: Jan
authors: J
authors: Grimm
authors: Neurimmune, Schlieren-Zurich 8952, Switzerland.|Institute for Regenerative Medicine, University of Zurich, Zurich 8952, Switzerland.
authors: Christoph
authors: C
authors: Hock
authors: Neurimmune, Schlieren-Zurich 8952, Switzerland.|Institute for Regenerative Medicine, University of Zurich, Zurich 8952, Switzerland.
authors: Roger M
authors: RM
authors: Nitsch
authors: Biogen, Cambridge, Massachusetts 02142, USA.
authors: Alfred
authors: A
authors: Sandrock
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D000682:Amyloid / Q000187:drug effects / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D017326:Clinical Trials, Phase III as Topic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D008954:Models, Biological; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000188:drug therapy; D012995:Solubility
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D061067:Antibodies, Monoclonal, Humanized; C000600266:aducanumab