Autoantibody-catalyzed hydrolysis of amyloid beta peptide

作者：Taguchi Hiroaki; Planque Stephanie; Nishiyama Yasuhiro; Symersky Jindrich; Boivin Stephane; Szabo Paul; Friedland Robert P; Ramsland Paul A; Edmundson Allen B; Weksler Marc E; Paul Sudhir

来源：Journal of Biological Chemistry, 2008, 283(8): 4714-4722.

DOI：10.1074/jbc.M707983200

We describe IgM class human autoantibodies that hydrolyze amyloid beta peptide 1-40 (A beta 40). A monoclonal IgM from a patient with Waldenstrom's macroglobulinemia hydrolyzed A beta 40 at the Lys-28 -Gly-29 bond and Lys-16 - Ala-17 bonds. The catalytic activity was inhibited stoichiometrically by an electrophilic serine protease inhibitor. Treatment with the catalytic IgM blocked the aggregation and toxicity of A beta 40 in neuronal cell cultures. IgMs purified from the sera of patients with Alzheimer disease (AD) hydrolyzed A beta 40 at rates superior to IgMs from age-matched humans without dementia. IgMs from non-elderly humans expressed the least catalytic activity. The reaction rate was sufficient to afford appreciable degradation at physiological A beta and IgM concentrations found in peripheral circulation. Increased A beta concentrations in the AD brain are thought to induce neurodegenerative effects. Peripheral administration of A beta binding antibodies has been suggested as a potential treatment of AD. Our results suggest that catalytic IgM autoantibodies can help clear A beta, and they open the possibility of using catalytic Abs for AD immunotherapy.

• 出版日期2008-2-22
• 单位河北医科大学