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Monoclonal antibodies against large oval aggregates of Aβ1–42

Paper ID Volume ID Publish Year Pages File Format Full-Text
20839 43193 2013 5 PDF Available
Title
Monoclonal antibodies against large oval aggregates of Aβ1–42
Abstract

Abnormal cerebral accumulation of amyloid beta protein1–42 (Aβ1–42) is one of the hallmarks of Alzheimer's disease (AD). Aβ1–42 aggregates exist in two distinct forms: fibrils that are composed of highly ordered β-sheets and amorphous aggregates that differ in size and toxicity. Here, we generated large oval aggregates (LOA) 369 ± 81 nm and 224 ± 92 nm in size on their major and minor axes, respectively, as measured by tapping-mode atomic force microscopy. LOA were produced by slow rotation of high concentrations (0.22 mM, 1.0 mg/mL) of Aβ1–42 for 16 h at 37°C in the presence of 2.2 mM Aβ16–20, which prevents the fibril formation, and purified with 0.22-μm filters. Analysis with thioflavin T showed that LOA have little β-sheet structure on their surfaces. Monoclonal antibodies that react with LOA, but not the fibril forms, were screened from 960 mouse hybridoma cell lines, and seven antibodies consisting of four IgG and three IgM antibodies were obtained. Four IgG monoclonal antibodies showed cross-reactivity of <10% against the monomer and fibril forms and amorphous aggregates that passed through 0.22-μm filters. Among the four antibodies, the antibody that was designated as 31-2 exhibited the highest reactivity against LOA and showed the lowest reactivity against the fibril forms. On the basis of these results, a unique epitope on the surface of LOA was suggested. The 31-2 antibody may be useful for future basic research and therapeutic applications for AD.

Keywords
Aβ1–42; Monoclonal antibody; Large oval aggregates; Amorphous aggregates; Fibril form
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 115, Issue 2, February 2013, Pages 216–220
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us