Aβ∗56 is a stable oligomer that impairs memory function in mice

Peng Liu, Ian P. Lapcinski, Chris J.W. Hlynialuk, Elizabeth L. Steuer, Thomas J. Loude, Samantha L. Shapiro, Lisa J. Kemper, Karen H. Ashe

Research output: Contribution to journalArticlepeer-review


Amyloid-β (Aβ) oligomers consist of fibrillar and non-fibrillar soluble assemblies of the Aβ peptide. Aβ∗56 is a non-fibrillar Aβ assembly that is linked to memory deficits. Previous studies did not decipher specific forms of Aβ present in Aβ∗56. Here, we confirmed the memory-impairing characteristics of Aβ∗56 and extended its biochemical characterization. We used anti-Aβ(1-x), anti-Aβ(x-40), anti-Aβ(x-42), and A11 anti-oligomer antibodies in conjunction with western blotting, immunoaffinity purification, and size-exclusion chromatography to probe aqueous brain extracts from Tg2576, 5xFAD, and APP/TTA mice. In Tg2576, Aβ∗56 is a ∼56-kDa, SDS-stable, A11-reactive, non-plaque-dependent, water-soluble, brain-derived oligomer containing canonical Aβ(1-40). In 5xFAD, Aβ∗56 is composed of Aβ(1-42), whereas in APP/TTA, it contains both Aβ(1-40) and Aβ(1-42). When injected into the hippocampus of wild-type mice, Aβ∗56 derived from Tg2576 mice impairs memory. The unusual stability of this oligomer renders it an attractive candidate for studying relationships between molecular structure and effects on brain function.

Original languageEnglish (US)
Article number109239
Issue number3
StatePublished - Mar 15 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors


  • Biochemistry
  • Neuroscience

PubMed: MeSH publication types

  • Journal Article


Dive into the research topics of 'Aβ∗56 is a stable oligomer that impairs memory function in mice'. Together they form a unique fingerprint.

Cite this