Abstract: Binding polypeptides (e.g., antibodies and antigen-binding fragments thereof) that specifically bind one or more species of soluble, AD brain-derived synaptotoxic amyloid beta (A?) without binding to classical monomeric, protofibrillar or fibrillar A?, are provided. Pharmaceutical compositions comprising binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided. Methods of making binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided. Methods of treating Alzheimer's disease using binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided. Methods of reducing one or more symptoms of Alzheimer's disease using binding polypeptides that specifically bind one or more species of soluble, synaptotoxic A? are provided.

Abstract: Novel compositions containing an amyloid-? peptide (A?) and methods of using these compositions for treating and preventing A? protein related (e.g., an amyloid fibril) disorders such as Alzheimer's disease are described herein. Also described herein are methods for identifying a vaccine, and methods of vaccinating a patient with an A? peptide composition identified using the methods described herein.