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 Ruggeri, Michele Perni, Ryan Limbocker, Gabriella T Heller, Tomas Sneideris, Tom Scheidt, Benedetta Mannini, Johnny Habchi, Steven Lee, Patricia C Salinas, Tuomas Knowles, Christopher M Dobson & Michele Vendruscolo
Protein misfolding and aggregation is the hallmark of numerous human disorders, including Alzheimer's disease. This process involves the formation of transient and heterogeneous soluble oligomers, some of which are highly cytotoxic. A major challenge for the development of effective diagnostic and therapeutic tools is thus the detection and quantification of these elusive oligomers. Here, to address this problem, we develop a two-step rational design method for the discovery of oligomer-specific antibodies. The first step consists...
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