Back

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.

2023-03-21 neuroscience
10.1101/2023.03.20.533414 bioRxiv
Show 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.

Matching journals

The top 10 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.