Rational design of a conformation-specific antibody for the quantification of Aβ oligomers
Francesco A. Aprile, Pietro Sormanni, Marina Podpolny, Shianne Chhangur, Lisa-Maria Needham, Francesco Simone Ruggeri, Michele Perni, Ryan Limbocker, Gabriella T. Heller, Tomas Šneideris, Tom Scheidt, Benedetta Mannini, Johnny Habchi, Steven F. Lee, Patricia C. Salinas, Tuomas P. J. Knowles, Christopher M. Dobson, Michele Vendruscolo
Abstract
Significance The accurate quantification of the amounts of small oligomeric assemblies formed by the amyloid β (Aβ) peptide represents a major challenge in the Alzheimer’s field. There is therefore great interest in the development of methods to specifically detect these oligomers by distinguishing them from larger aggregates. The availability of these methods will enable the development of effective diagnostic and therapeutic interventions for this and other diseases related to protein misfolding and aggregation. We describe here a single-domain antibody able to selectively quantify oligomers of the Aβ peptide in isolation and in complex protein mixtures from animal models of disease.