Lee EB, Leng LZ, Zhang B, Kwong L, Trojanowski JQ, Abel T et al. Targeting amyloid-beta peptide (Abeta) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Abeta precursor protein (APP) transgenic mice. J Biol Chem 281: 4292-4299

Biology, William Penn University, Filadelfia, Pennsylvania, United States
Journal of Biological Chemistry (Impact Factor: 4.57). 03/2006; 281(7):4292-9. DOI: 10.1074/jbc.M511018200
Source: PubMed


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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Available from: Ted Abel, Jan 03, 2016
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    • "Thus, YAP1802 is likely to affect toxicity by reducing the level of toxic Aβ 42 oligomers. We also used NAB61 antibody, which was reported to preferentially recognize toxic Aβ oligomers in AD patients [35] and HDEL-Aβ 42 in yeast [24]. Indeed, while Sup35C antibody detected only monomers in Aβ 42 m2-RF cells expressing the Aβ 42 aggregation-deficient mutation (Figure S1 ), NAB61 did not recognize Aβ 42 m2-RF monomers although it detected a species the size of dimers. "

    Full-text · Article · Feb 2016
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    • "A wide variety of such oligomer-specific antibodies is now available. For example, NAB61 is a monoclonal antibody specific for Aβ oligomers developed by synthesizing oligomeric aggregates from nitrated Aβ and using them as antigens [146]. Antibodies NU1, NU2 and NU4 used small β-sheet rich Aβ oligomers as antigens [147] [148] [149]. "
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    ABSTRACT: Protein misfolding and aggregation are known to play a crucial role in a number of important human diseases (Alzheimer's, Parkinson's, prion, diabetes, cataracts, etc.) as well as in a multitude of physiological processes. Protein aggregation is a highly complex process resulting in a variety of aggregates with different structures and morphologies. Oligomeric protein aggregates (amyloid oligomers) are formed as both intermediates and final products of the aggregation process. They are believed to play an important role in many protein aggregation-related diseases, and many of them are highly cytotoxic. Due to their instability and structural heterogeneity, information about structure, mechanism of formation, and physiological effects of amyloid oligomers is sparse. This review attempts to summarize the existing information on the major properties of amyloid oligomers. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Jul 2015 · FEBS letters
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    • "To evaluate the relevance of our findings to AD, we estimated the volume of human cortex occupied by type 2 Abo in AD, using two different methods. One method depended on immunohistological data of tissue stained with the Abo-specific antibody NAB-61 (Lee et al., 2006), which we inferred selectively recognizes type 2 Abo and amyloid fibrils from its almost exclusive staining of neuritic plaques (dense-core plaques associated with neuritic abnormalities [Serrano-Pozo et al., 2011]). The average volume of AD cortex occupied by Ab assemblies detected using NAB-61 was $5% (Perez-Nievas et al., 2013). "
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    ABSTRACT: The accumulation of amyloid-β (Aβ) as amyloid fibrils and toxic oligomers is an important step in the development of Alzheimer's disease (AD). However, there are numerous potentially toxic oligomers and little is known about their neurological effects when generated in the living brain. Here we show that Aβ oligomers can be assigned to one of at least two classes (type 1 and type 2) based on their temporal, spatial, and structural relationships to amyloid fibrils. The type 2 oligomers are related to amyloid fibrils and represent the majority of oligomers generated in vivo, but they remain confined to the vicinity of amyloid plaques and do not impair cognition at levels relevant to AD. Type 1 oligomers are unrelated to amyloid fibrils and may have greater potential to cause global neural dysfunction in AD because they are dispersed. These results refine our understanding of the pathogenicity of Aβ oligomers in vivo. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
    Full-text · Article · Jun 2015 · Cell Reports
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