Bapineuzumab captures the N-terminus of the Alzheimer's disease amyloid-beta peptide in a helical conformation.
Bapineuzumab is a humanized antibody developed by Pfizer and Johnson &
Johnson targeting the amyloid (Aβ) plaques that underlie Alzheimer's disease
neuropathology. Here we report the crystal structure of a Fab-Aβ peptide
complex that reveals Bapineuzumab surprisingly captures Aβ in a monomeric
helical conformation at the N-terminus. Microscale thermophoresis suggests that
the Fab binds soluble Aβ(1-40) with a K(D) of 89 (±9) nM. The structure
explains the antibody's exquisite selectivity for particular Aβ species and why
it cannot recognize N-terminally modified or truncated Aβ peptides.