Specific Amyloid β Clearance by a Catalytic Antibody Construct

Classical immunization methods do not generate catalytic antibodies (catabodies), but recent findings suggest that the innate antibody repertoire is a rich catabody source. We describe the specificity and amyloid (A)-clearing effect of a catabody construct engineered from innate immunity principles. The catabody recognized the A C terminus noncovalently and hydrolyzed A rapidly, with no reactivity to the A precursor protein, transthyretin amyloid aggregates, or irrelevant proteins containing the catabody-sensitive A dipeptide unit. The catabody dissolved preformed A aggregates and inhibited A aggregation more potently than an A-binding IgG. Intravenous catabody treatment reduced brain A deposits in a mouse Alzheimer disease model without inducing microgliosis or microhemorrhages. Specific A hydrolysis appears to be an innate immune function that could be applied for therapeutic A removal.