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Cell Rep. 2015 Jun 23;11(11):1760-71. doi: 10.1016/j.celrep.2015.05.021. Epub 2015 Jun 4.

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

Author information

1
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA.
2
N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA; UMN Academic Health Center Biological Materials Procurement Network, University of Minnesota, Minneapolis, MN 55455, USA.
3
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
4
Departments of Neuroscience, Neurology and Neurosurgery, Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
5
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
6
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA; Geriatric Research, Education and Clinical Center (GRECC), VA Medical Center, Minneapolis, MN 55417, USA.
7
Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA; N. Bud Grossman Center for Memory Research and Care, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Geriatric Research, Education and Clinical Center (GRECC), VA Medical Center, Minneapolis, MN 55417, USA. Electronic address: hsiao005@umn.edu.

Abstract

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.

PMID:
26051935
PMCID:
PMC4494129
DOI:
10.1016/j.celrep.2015.05.021
[Indexed for MEDLINE]
Free PMC Article

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