Targeting Amyloid-β Peptide (Aβ) Oligomers by Passive Immunization with a Conformation-selective Monoclonal Antibody Improves Learning and Memory in Aβ Precursor Protein (APP) Transgenic Mice

Edward B Lee; Lewis Z Leng; Bin Zhang; Linda Kwong; John Q Trojanowski; Ted Abel; Virginia M.-Y Lee

doi:10.1074/jbc.M511018200

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Targeting Amyloid-β Peptide (Aβ) Oligomers by Passive Immunization with a Conformation-selective Monoclonal Antibody Improves Learning and Memory in Aβ Precursor Protein (APP) Transgenic Mice

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Targeting Amyloid-β Peptide (Aβ) Oligomers by Passive Immunization with a Conformation-selective Monoclonal Antibody Improves Learning and Memory in Aβ Precursor Protein (APP) Transgenic Mice

Edward B Lee, Lewis Z Leng, Bin Zhang, Linda Kwong, John Q Trojanowski, Ted Abel and Virginia M.-Y Lee

The Journal of biological chemistry, Vol.281(7), pp.4292-4299

02/17/2006

DOI: 10.1074/jbc.M511018200

PMID: 16361260

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Abstract

Passive immunization of murine models of Alzheimer disease amyloidosis reduces amyloid-β peptide (Aβ) levels and improves cognitive function. To specifically address the role of Aβ oligomers in learning and memory, we generated a novel monoclonal antibody, NAB61, that preferentially recognizes a conformational epitope present in dimeric, small oligomeric, and higher order Aβ structures but not full-length amyloid-β precursor protein or C-terminal amyloid-β precursor protein fragments. NAB61 also recognized a subset of brain Aβ deposits, preferentially mature senile plaques, and amyloid angiopathy. Using NAB61 as immunotherapy, we showed that aged Tg2576 transgenic mice treated with NAB61 displayed significant improvements in spatial learning and memory relative to control mice. These data implicated Aβ oligomers as a pathologic substrate for cognitive decline in Alzheimer disease.

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Title: Subtitle: Targeting Amyloid-β Peptide (Aβ) Oligomers by Passive Immunization with a Conformation-selective Monoclonal Antibody Improves Learning and Memory in Aβ Precursor Protein (APP) Transgenic Mice
Creators: Edward B Lee - Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Lewis Z Leng - Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Bin Zhang - Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Linda Kwong - Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
John Q Trojanowski - Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Ted Abel - Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Virginia M.-Y Lee - Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.281(7), pp.4292-4299
DOI: 10.1074/jbc.M511018200
PMID: 16361260
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 02/17/2006
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065733402771

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