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The most common type of dementia is Alzheimer's disease. Recent data from the pharmaceutical company Eli Lilly claims that the monoclonal antibody Solanezumab can slow the rate of the disease’s progression.

Alzheimer’s is characterised by the accumulation in the brain of proteinaceous masses, called amyloid plaques. These plaques are rich in a protein called amyloid beta which exists in several conformations in the body. In Alzheimer's it forms neurotoxic fibrils which exist in mostly beta-strand conformation. Several models of these fibrils are present in the PDB archive.

Model of an amyloid fibril () shown as sticks with the di-phenylalanine motif in magenta.

Solanezumab recognizes amyloid beta and the structure of the antibody in complex with an amyloid beta peptide was published earlier this year in Scientific Reports and deposited in the PDB ().  Unlike some other anti-amyloid beta antibodies, Solanezumab binds to the core region of amyloid beta which is involved in forming amyloid fibrils.

Between the antibody and amyloid beta peptide, there are extensive contacts extending over 10 amino acids of the amyloid beta peptide. These bury nearly 1000Ã…² of surface, significantly more than usual for antibody-peptide complexes. In particular, Solanezumab recognises two phenylalanines, coloured magenta in the accompanying images, which are buried deep in the antigen-binding cleft of the antibody. 

Detail of the Solanezumab binding site for amyloid beta peptide. The antibody has an orange surface with the peptide shown as sticks. The central di-phenylalanine motif is coloured magenta.

Unfortunately, the antibody also cross-reacts with other proteins in the body which have this di-phenylalanine motif. Knowledge of the structure of the antibody-peptide complex shows exactly how it binds to amyloid beta and could help design improved Alzheimer's drugs with reduced cross-reactivity.

The paper describing PDB entry , by Crespi et al., is published in Scientific Reports