Internal medicine

Pathology

Neuroscience

Adverse effect

Immunotherapy

Disease

Dementia

Monoclonal antibody

Biology

Psychiatry

Antibody

Immunology

Amyloid (mycology)

Human brain

Neurodegeneration

Humanized antibody

Tolerability

Neurotoxicity

Biomarker

Toxicity

Alzheimer's disease

Biochemistry

Medicine

Immune system

Pharmacology

Nature

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. Aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ, reduces soluble and insoluble Aβ in the brain, an action accompanied by a dose-dependent slowing of clinical decline in treated patients. Aducanumab is a recombinant human monoclonal antibody that selectively targets the amyloid-β (Aβ) peptide aggregates thought to play a part in the neurodegenerative process in Alzheimer's disease. Several Alzheimer's disease drugs have failed in development in recent years — including other anti-amyloid antibodies — so there is intense interest in any new developments. A new study reports interim results from a clinical trial of monthly infusions of aducanumab in subjects with prodromal or mild Alzheimer's disease. Treatment with aducanumab reduced brain Aβ plaques, an action accompanied by a dose-dependent slowing of clinical decline. The trial data support further development of aducanumab as an Aβ-removing therapy.

The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease