Specific Amyloid {beta} Clearance by a Catalytic Antibody Construct [Neurobiology]

February 27th, 2015 by Planque, S. A., Nishiyama, Y., Sonoda, S., Lin, Y., Taguchi, H., Hara, M., Kolodziej, S., Mitsuda, Y., Gonzalez, V., Sait, H. B. R., Fukuchi, K.-i., Massey, R. J., Friedland, R. P., O'Nuallain, B., Sigurdsson, E. M., Paul, S.

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