Aducanumab

Alzheimer's disease is a neurodegenerative disease. Part of the pathology of Alzheimer's disease is the presence of plaques forming extracellularly in the brain. These plaques are mostly composed of amyloid-β, a peptide of varying length formed by the cleavage of the amyloid precursor protein. The "amyloid cascade hypothesis" suggests that the accumulation of amyloid-β oligopeptides in the brain drives the pathogenesis of Alzheimer's disease.

Aducanumab is a monoclonal IgG1 antibody that binds to amyloid-β at amino acids 3-7. The amyloid-β residues Phe4, His6, Glu3, and Arg5 are responsible for the majority of the contact between amyloid-β and aducanumab's Fab region. Data from studies in mice and humans shows aducanumab treatment reduces amyloid-β, however human trials show non-significant changes in amyloid-β40 and amyloid-β42 across a dose range of 0.3-30 mg/kg and an increase in amyloid-β40 and amyloid-β42 at 60 mg/kg.

Aducanumab treatment is associated with slowing the rate of progression of Alzheimer's disease, based on Mini-Mental State Examination, Clinical Dementia Rating, and levels of p-tau in the cerebrospinal fluid.