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bioRxiv · 10.1101/2023.03.20.533414

Abeta*56 is a stable oligomer that correlates with age-related memory loss in Tg2576 mice

Ashe, K.·Liu, P.·Lapcinski, I.·Shapiro, S.·Kemper, L.
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Abstract

Amyloid-{beta} (A{beta}) oligomers consist of fibrillar and non-fibrillar soluble assemblies of the A{beta} peptide. Tg2576 human amyloid precursor protein (APP)-expressing transgenic mice modeling Alzheimers disease produce A{beta}*56, a non-fibrillar A{beta} assembly that has been shown by several groups to relate more closely to memory deficits than plaques. Previous studies did not decipher specific forms of A{beta} present in A{beta}*56. Here, we confirm and extend the biochemical characterization of A{beta}*56. We used anti-A{beta}(1-x), anti-A{beta}(x-40), and A11 anti-oligomer antibodies in conjunction with western blotting, immunoaffinity purification, and size-exclusion chromatography to probe aqueous brain extracts from Tg2576 mice of different ages. We found that A{beta}*56 is a [~]56-kDa, SDS-stable, A11-reactive, non-plaque-related, water-soluble, brain-derived oligomer containing canonical A{beta}(1-40) that correlates with age-related memory loss. The unusual stability of this high molecular-weight oligomer renders it an attractive candidate for studying relationships between molecular structure and effects on brain function.

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Ashe, K., Liu, P., Lapcinski, I., Shapiro, S., Kemper, L.. 2023-03-21. Abeta*56 is a stable oligomer that correlates with age-related memory loss in Tg2576 mice. https://doi.org/10.1101/2023.03.20.533414

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