Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration

Peng Liu; Miranda N. Reed; Linda A. Kotilinek; Marianne K.O. Grant; Colleen L. Forster; Wei Qiang; Samantha L. Shapiro; John H. Reichl; Angie C.A. Chiang; Joanna L. Jankowsky; Carrie M. Wilmot; James P. Cleary; Kathleen R. Zahs; Karen H. Ashe

doi:10.1016/j.celrep.2015.05.021

Cell Reports (Jun 2015)

Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration

Peng Liu,
Miranda N. Reed,
Linda A. Kotilinek,
Marianne K.O. Grant,
Colleen L. Forster,
Wei Qiang,
Samantha L. Shapiro,
John H. Reichl,
Angie C.A. Chiang,
Joanna L. Jankowsky,
Carrie M. Wilmot,
James P. Cleary,
Kathleen R. Zahs,
Karen H. Ashe

Affiliations

Peng Liu: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Miranda N. Reed: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Linda A. Kotilinek: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Marianne K.O. Grant: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Colleen L. Forster: N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA
Wei Qiang: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Samantha L. Shapiro: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
John H. Reichl: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Angie C.A. Chiang: Departments of Neuroscience, Neurology and Neurosurgery, Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA
Joanna L. Jankowsky: Departments of Neuroscience, Neurology and Neurosurgery, Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA
Carrie M. Wilmot: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA
James P. Cleary: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Kathleen R. Zahs: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA
Karen H. Ashe: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA

DOI: https://doi.org/10.1016/j.celrep.2015.05.021
Journal volume & issue: Vol. 11, no. 11
pp. 1760 – 1771

Abstract

Read online

The accumulation of amyloid-β (Aβ) as amyloid fibrils and toxic oligomers is an important step in the development of Alzheimer’s disease (AD). However, there are numerous potentially toxic oligomers and little is known about their neurological effects when generated in the living brain. Here we show that Aβ oligomers can be assigned to one of at least two classes (type 1 and type 2) based on their temporal, spatial, and structural relationships to amyloid fibrils. The type 2 oligomers are related to amyloid fibrils and represent the majority of oligomers generated in vivo, but they remain confined to the vicinity of amyloid plaques and do not impair cognition at levels relevant to AD. Type 1 oligomers are unrelated to amyloid fibrils and may have greater potential to cause global neural dysfunction in AD because they are dispersed. These results refine our understanding of the pathogenicity of Aβ oligomers in vivo.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal