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

Research output: Contribution to journalArticle

70 Citations (Scopus)

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. Liu et al. classify brain-derived amyloid-β oligomers into type 1 and type 2. Type 2, but not type 1, oligomers have a spatiotemporal and structural relationship with amyloid plaques. Highly abundant type 2 oligomers do not impair cognition in situ, possibly due to spatial sequestration around plaques.

Original languageEnglish (US)
Pages (from-to)1760-1771
Number of pages12
JournalCell Reports
Volume11
Issue number11
DOIs
StatePublished - Jun 23 2015

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Oligomers
Amyloid
Alzheimer Disease
Poisons
Amyloid Plaques
Cognition
Brain
Virulence

Cite this

Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration. / Liu, Peng; Reed, Miranda N.; Kotilinek, Linda A.; Grant, Marianne K.O.; Forster, Colleen L.; Qiang, Wei; Shapiro, Samantha L.; Reichl, John H.; Chiang, Angie C.A.; Jankowsky, Joanna L.; Wilmot, Carrie M; Cleary, James P; Zahs, Kathleen R; Ashe, Karen H.

In: Cell Reports, Vol. 11, No. 11, 23.06.2015, p. 1760-1771.

Research output: Contribution to journalArticle

Liu, P, Reed, MN, Kotilinek, LA, Grant, MKO, Forster, CL, Qiang, W, Shapiro, SL, Reichl, JH, Chiang, ACA, Jankowsky, JL, Wilmot, CM, Cleary, JP, Zahs, KR & Ashe, KH 2015, 'Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration', Cell Reports, vol. 11, no. 11, pp. 1760-1771. https://doi.org/10.1016/j.celrep.2015.05.021
Liu, Peng ; Reed, Miranda N. ; Kotilinek, Linda A. ; Grant, Marianne K.O. ; Forster, Colleen L. ; Qiang, Wei ; Shapiro, Samantha L. ; Reichl, John H. ; Chiang, Angie C.A. ; Jankowsky, Joanna L. ; Wilmot, Carrie M ; Cleary, James P ; Zahs, Kathleen R ; Ashe, Karen H. / Quaternary Structure Defines a Large Class of Amyloid-β Oligomers Neutralized by Sequestration. In: Cell Reports. 2015 ; Vol. 11, No. 11. pp. 1760-1771.
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