The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

  title={The antibody aducanumab reduces A$\beta$ plaques in Alzheimer’s disease},
  author={Jeff Sevigny and Ping Chiao and Thierry Bussiere and Paul H Weinreb and Leslie Williams and Marcel Maier and Robert W. Dunstan and Stephen P. Salloway and Tianle Chen and Yan Ling and John O’Gorman and Fang Qian and Mahin F. Arastu and Mingwei Li and Sowmya Chollate and Melanie S. Brennan and Omar Quintero-Monzon and Robert H. Scannevin and H. Moore Arnold and Thomas M. Engber and Kenneth J. Rhodes and Jim Ferrero and Yaming Hang and Alvydas Mikulskis and Jan Grimm and Christoph Hock and Roger M. Nitsch and Alfred W. Sandrock},
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… 

Aducanumab reduces Aβ plaques in Alzheimer's disease

  • D. Vaillancourt
  • Medicine, Biology
    Movement disorders : official journal of the Movement Disorder Society
  • 2016
Evidence is provided that aducanumab penetrates the brain and decreases amyloid plaques in patients with AD during a 54-week period, and the importance of having an imaging marker in Parkinson’s disease that can be used to assess a potential therapy is shown.

Alzheimer disease: Anti-Aβ antibody treatment shows promise in Alzheimer disease

  • I. Fyfe
  • Biology
    Nature Reviews Neurology
  • 2016
A robust time-dependent and dose-dependent reduction in amyloid burden is found and is probably the key reason for the hint of clinical efficacy on the exploratory cognitive endpoints, says Sandrock.

Aducanumab: a review of the first approved amyloid-targeting antibody for Alzheimer’s disease

While one of its phase III clinical trials demonstrated a reduction in the cognitive decline, the other phase III trial has failed to do so, so its efficacy is still uncertain and the results of a further trial are needed to shed more light on this.

Aducanumab Therapy to Treat Alzheimer's Disease: A Narrative Review

Infusion of aducanumab at a higher dose resulted in a modest slowing of cognitive decline among patients with mild cognitive impairment or early-onset AD dementia, making it the first disease-modifying therapy approved for the treatment of AD.

Immunotherapies for Alzheimer’s Disease—A Review

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that falls under the umbrella of dementia and is characterised by the presence of highly neurotoxic amyloid-beta (Aβ) plaques and

The progress of Aduhelm in the treatment for Alzheimer's disease (AD)

Clinical trials data show that Aduhelm drug is associated with significant reductions in A-PET signal in the brains of Alzheimer's disease patients, but Adu Helm seems to reduce MMSE and CDR-SB deterioration in a dose-dependent way, and controversy over the efficacy and/or safety of Aduheim in Alzheimer's Disease is introduced.

Alzheimer disease neuropathology in a patient previously treated with aducanumab

This case report is the first to provide Amyloid PET and neuropathologic evidence substantiating the impact of aducanumab to reduce Aβ plaque neuropathology in a patient with AD.

Quantitative systems pharmacology model for Alzheimer’s disease to predict the effect of aducanumab on brain amyloid

A quantitative systems pharmacology model describing the production, aggregation, clearance, and transport of Aβ as well as the mechanism of action for the drug was developed to understand the relationship between aducanumab dosing regimens and changes of different Aβ species, particularly plaques in the brain.

Drug candidates in clinical trials for Alzheimer’s disease

The findings from recent clinical trials are systemically reviewed to provide a comprehensive review of novel therapeutic compounds in the treatment and prevention of AD.

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer’s Disease

ACU193 is described, the first A βO-selective immunotherapeutic to enter human clinical trials and the first positioned to test the AβO hypothesis of AD.



Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease.

Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability in patients with mild Alzheimer's disease.

Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease

Results indicate that antibodies can cross the blood–brain barrier to act directly in the central nervous system and should be considered as a therapeutic approach for the treatment of Alzheimer disease and other neurological disorders.

Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab.

Gantenerumab treatment resulted in a dose-dependent reduction in brain amyloid level, possibly through an effector cell-mediated mechanism of action.

The therapeutics of Alzheimer's disease: Where we stand and where we are heading

  • D. Selkoe
  • Biology, Psychology
    Annals of neurology
  • 2013
The pace of recent developments augurs well for 1 or more experimental agents being shown to slow cognitive decline without major side effects, however, research funding from all sources will need to increase dramatically and soon to stave off the approaching tsunami of AD.

Generation of antibodies specific for β-amyloid by vaccination of patients with Alzheimer disease

Findings indicate that vaccination of AD patients with Aβ42 induces antibodies that have a high degree of selectivity for the pathogenic target structures, and whether vaccination to produce antibodies against β-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.

Robust Amyloid Clearance in a Mouse Model of Alzheimer's Disease Provides Novel Insights into the Mechanism of Amyloid-β Immunotherapy

It is demonstrated that anti-Aβ immunotherapy combined with suppression of Aβ synthesis allows significant removal of antecedent deposits, and suggested that combining two therapeutic approaches currently in clinical trials may improve neuropathological outcome over either alone.

Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease.

Bapineuzumab did not improve clinical outcomes in patients with Alzheimer's disease, despite treatment differences in biomarkers observed in APOE ε4 carriers.

Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory

It is concluded that soluble Aβ oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.

The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

The evidence supporting toxic Aβ oligomers as drivers of neurodegeneration is reviewed and some suggestions that might facilitate progress are made to facilitate progress in this complex field.