The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

@article{Sevigny2016TheAA,
  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},
  journal={Nature},
  year={2016},
  volume={537},
  pages={50-56}
}
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… 

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References

SHOWING 1-10 OF 40 REFERENCES

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

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

Consequence of Abeta immunization on the vasculature of human Alzheimer's disease brain.

TLDR
The findings are consistent with the hypothesis that Abeta immunization results in solubilization of plaque Abeta42 which, at least in part, exits the brain via the perivascular pathway, causing a transient increase in the severity of CAA.

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

TLDR
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.

TLDR
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
TLDR
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

TLDR
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.

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

TLDR
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

TLDR
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

TLDR
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.