Abstract: Provided are compositions and methods for expressing a plurality of target polypeptides at a high level in mammalian host cells. Each target polypeptide is encoded on a polynucleotide comprising a nucleotide sequence encoding a unique cell surface marker polypeptide and a nucleotide sequence encoding a unique target polypeptide, wherein both the nucleotide sequence encoding the unique cell surface marker polypeptide and the nucleotide sequence encoding the unique target polypeptide are transcribed on the same mRNA. Each mammalian host cell comprises a plurality of different polynucleotides, such that the cell is capable of expressing a plurality of unique target polypeptides and a plurality of unique cell surface marker polypeptides. In certain embodiments, the plurality of unique cell surface marker polypeptides are variants of CD52. The compositions and methods are useful for expressing multimeric target proteins, e.g., crossover dual-variable domain (CODV) triabodies.

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.