Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia

Brian J. Tabner, Omar Ali El-Agnaf, Stuart Turnbull, Matthew J. German, Katerina E. Paleologou, Yoshihito Hayashi, Leanne J. Cooper, Nigel J. Fullwood, David Allsop

Research output: Contribution to journalArticle

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Abstract

Alzheimer disease and familial British dementia are neurodegenerative diseases that are characterized by the presence of numerous amyloid plaques in the brain. These lesions contain fibrillar deposits of the β-amyloid peptide (Aβ) and the British dementia peptide (ABri), respectively. Both peptides are toxic to cells in culture, and there is increasing evidence that early "soluble oligomers" are the toxic entity rather than mature amyloid fibrils. The molecular mechanisms responsible for this toxicity are not clear, but in the case of Aβ, one prominent hypothesis is that the peptide can induce oxidative damage via the formation of hydrogen peroxide. We have developed a reliable method, employing electron spin resonance spectroscopy in conjunction with the spin-trapping technique, to detect any hydrogen peroxide generated during the incubation of Aβ and other amyloidogenic peptides. Here, we monitored levels of hydrogen peroxide accumulation during different stages of aggregation of Aβ-(1-40) and ABri and found that in both cases it was generated as a short "burst" early on in the aggregation process. Ultrastructural studies with both peptides revealed that structures resembling "soluble oligomers" or "protofibrils" were present during this early phase of hydrogen peroxide formation. Mature amyloid fibrils derived from Aβ-(1-40) did not generate hydrogen peroxide. We conclude that hydrogen peroxide formation during the early stages of protein aggregation may be a common mechanism of cell death in these (and possibly other) neurodegenerative diseases.

Original languageEnglish
Pages (from-to)35789-35792
Number of pages4
JournalJournal of Biological Chemistry
Volume280
Issue number43
DOIs
Publication statusPublished - 28 Oct 2005
Externally publishedYes

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Amyloid
Hydrogen Peroxide
Alzheimer Disease
Agglomeration
Peptides
Abrus
Neurodegenerative diseases
Poisons
Amyloid Plaques
Oligomers
Neurodegenerative Diseases
Electron spin resonance spectroscopy
Spin Trapping
Electron Spin Resonance Spectroscopy
Cell death
Toxicity
Dementia
Familial British Dementia
Brain
Cell Death

ASJC Scopus subject areas

  • Biochemistry

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Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. / Tabner, Brian J.; Ali El-Agnaf, Omar; Turnbull, Stuart; German, Matthew J.; Paleologou, Katerina E.; Hayashi, Yoshihito; Cooper, Leanne J.; Fullwood, Nigel J.; Allsop, David.

In: Journal of Biological Chemistry, Vol. 280, No. 43, 28.10.2005, p. 35789-35792.

Research output: Contribution to journalArticle

Tabner, Brian J. ; Ali El-Agnaf, Omar ; Turnbull, Stuart ; German, Matthew J. ; Paleologou, Katerina E. ; Hayashi, Yoshihito ; Cooper, Leanne J. ; Fullwood, Nigel J. ; Allsop, David. / Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 43. pp. 35789-35792.
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