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, Jr.,
Samantha L. Shapiro,
Lisa J. Kemper,
Karen H. Ashe
Affiliations
Peng Liu
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding author
Ian P. Lapcinski
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Chris J.W. Hlynialuk
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Elizabeth L. Steuer
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Thomas J. Loude, Jr.
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Samantha L. Shapiro
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Lisa J. Kemper
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Karen H. Ashe
N. Bud Grossman Center for Memory Research and Care, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding author
Summary: 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.
