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 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.
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
Stephanie A
SA
Planque
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
Yasuhiro
Y
Nishiyama
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
Sari
S
Sonoda
the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016.
Yan
Y
Lin
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
Hiroaki
H
Taguchi
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
Mariko
M
Hara
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
Steven
S
Kolodziej
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030.
Yukie
Y
Mitsuda
the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016.
Veronica
V
Gonzalez
the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016.
Hameetha B R
HB
Sait
the Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, Illinois 61605.
Ken-ichiro
K
Fukuchi
Covalent Bioscience Inc., Houston, Texas 77054.
Richard J
RJ
Massey
the Department of Neurology, University of Louisville School of Medicine, Louisville, Kentucky 40202, and.
Robert P
RP
Friedland
the Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
Brian
B
O'Nuallain
the Departments of Neuroscience, Physiology, and Psychiatry, New York University School of Medicine, New York, New York 10016, Einar.Sigurdsson@nyumc.org.
Einar M
EM
Sigurdsson
From the Chemical Immunology Research Center, Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, Sudhir.Paul@uth.tmc.edu.
Sudhir
S
Paul
D000544:Alzheimer Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D017151:Antibodies, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D007113:Immunity, Innate; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry; D015202:Protein Engineering; D059748:Proteolysis; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D017151:Antibodies, Catalytic; D010446:Peptide Fragments; D011994:Recombinant Proteins; D057127:Single-Chain Antibodies
Alzheimer Disease; Amyloid-β (Abeta); Antibody Engineering; Catalytic Antibodies; Enzyme Catalysis; Immunotherapy; Innate Immunity; Light Chain Variable Domain; Neurotoxicity