An In Vitro Paradigm To Assess Potential Anti-A Beta Antibodies For Alzheimer'S Disease

Although the amyloid beta-protein (A beta) is believed to play an initiating role in Alzheimer's disease (AD), the molecular characteristics of the key pathogenic A beta forms are not well understood. As a result, it has proved difficult to identify optimal agents that target disease-relevant forms of A beta. Here, we combined the use of A beta-rich aqueous extracts of brain samples from AD patients as a source of human A beta and live-cell imaging of iPSC-derived human neurons to develop a bioassay capable of quantifying the relative protective effects of multiple anti-A beta antibodies. We report the characterization of 1C22, an aggregate-preferring murine anti-A beta antibody, which better protects against forms of A beta oligomers that are toxic to neurites than do the murine precursors of the clinical immunotherapeutics, bapineuzumab and solanezumab. These results suggest further examination of 1C22 is warranted, and that this bioassay maybe useful as a primary screen to identify yet more potent anti-A beta therapeutics.