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. 2021 Nov 4;15:752594. doi: 10.3389/fnins.2021.752594

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Copyright © 2021 Sanchez-Varo, Sanchez-Mejias, Fernandez-Valenzuela, De Castro, Mejias-Ortega, Gomez-Arboledas, Jimenez, Sanchez-Mico, Trujillo-Estrada, Moreno-Gonzalez, Baglietto-Vargas, Vizuete, Davila, Vitorica and Gutierrez.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Oligomeric forms of Aβ were located at the plaque periphery in both AD and APP/PS1 hippocampi. (A,B) Confocal double-fluorescent staining with Thioflavin-S [(A1,B1) green] and OC antibody [(A2,B2) red] revealed that oligomeric Aβ was mainly detected at the plaque periphery, depicting a halo around the fibrillar core in CA1 region of Braak VI brains (A3,B3). (C) Likewise, OC immunoreactivity showed the same disposition in plaques of 6-month-old APP/PS1 mouse hippocampus (C1–C3). (D) Aβ immunogold labeling (OC antibody) observed by TEM was found at the plaque border (red arrowheads; asterisk, Aβ deposit). Detail at higher magnifications in panel (E). Inset in panel (D). Detail of a plaque from CA1, immunostained for amyloid oligomers (OC antibody) in a semithin section from a 6-month-old APP/PS1 mouse. Counterstained with Harry’s hematoxylin. (F–H) Immunogold for 12–24 mers Aβ (NU-4) confirmed the presence of these specific amyloid oligomeric forms in the edge and peripheral threads of extracellular Aβ deposits (red arrowheads). Panel (H) depict details from panel (F). Scale bars, (A–C) 25 μm; (D,G–H) 1 μm, (E) 0.5 μm; (F) 2 μm.