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Detection of Amyloid β Oligomers with RNA Aptamers in AppNL-G-F/NL-G-F Mice: A Model of Arctic Alzheimer’s Disease

journal contribution
posted on 17.01.2021, 23:44 by Y Obata, K Murakami, T Kawase, K Hirose, Naotaka Izuo, T Shimizu, K Irie
Copyright © 2020 American Chemical Society. RNA aptamers have garnered attention for diagnostic applications due to their ability to recognize diverse targets. Oligomers of 42-mer amyloid β-protein (Aβ42), whose accumulation is relevant to the pathology of Alzheimer's disease (AD), are among the most difficult molecules for aptamer recognition because they are prone to aggregate in heterogeneous forms. In addition to designing haptens for in vitro selection of aptamers, the difficulties involved in determining their effect on Aβ42 oligomerization impede aptamer research. We previously developed three RNA aptamers (E22P-AbD4, -AbD31, and -AbD43) with high affinity for protofibrils (PFs) derived from a toxic Aβ42 dimer. Notably, these aptamers recognized diffuse staining, which likely originated from PFs or higher-order oligomers with curvilinear structures in a knock-in AppNL-G-F/NL-G-F mouse, carrying the Arctic mutation that preferentially induced the formation of PFs, in addition to a PS2Tg2576 mouse. To determine which oligomeric sizes were mainly altered by the aptamer, ion mobility-mass spectrometry (IM-MS) was carried out. One aptamer, E22P-AbD43, formed adducts with the Aβ42 monomer and dimer, leading to suppression of further oligomerization. These findings support the utility of these aptamers as diagnostics for AD.

Funding

We thank Dr. Takaomi C. Saido and Dr. Takashi Saito at RIKEN Brain Science Institute for providing AppNL-G-F/NL-G-F mice. This study was supported in part by the JSPS KAKENHI, grant numbers 22603006 to K.M., 16H06194 to K.M., and 26221202 to K.I. and K.M.

History

Publication Date

17/08/2020

Journal

ACS Omega

Volume

5

Issue

34

Pagination

7p. (p. 21531-21537)

Publisher

American Chemical Society

ISSN

2470-1343

Rights Statement

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