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Oligomeric and fibrillar species of beta-amyloid (Abeta42) both impair mitochondrial function in P301L tau transgenic mice

Eckert, A. and Hauptmann, S. and Scherping, I. and Meinhardt, J. and Rhein, V. and Dröse, S. and Brandt, U. and Fändrich, M. and Müller, W. E. and Götz, J.. (2008) Oligomeric and fibrillar species of beta-amyloid (Abeta42) both impair mitochondrial function in P301L tau transgenic mice. Journal of molecular medicine, Vol. 86, no. 11. pp. 1255-1267.

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Official URL: http://edoc.unibas.ch/dok/A6005522

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Abstract

We recently provided evidence for a mitochondrial dysfunction in P301L tau transgenic mice, a strain modeling the tau pathology of Alzheimer's disease (AD) and frontotemporal dementia (FTD). In addition to tau aggregates, the AD brain is further characterized by Abeta peptide-containing plaques. When we addressed the role of Abeta, this indicated a synergistic action of tau and Abeta pathology on the mitochondria. In the present study, we compared the toxicity of different Abeta42 conformations in light of recent studies suggesting that oligomeric rather than fibrillar Abeta might be the actual toxic species. Interestingly, both oligomeric and fibrillar, but not disaggregated (mainly monomeric) Abeta42 caused a decreased mitochondrial membrane potential in cortical brain cells obtained from FTD P301L tau transgenic mice. This was not observed with cerebellar preparations indicating selective vulnerability of cortical neurons. Furthermore, we found reductions in state 3 respiration, the respiratory control ratio, and uncoupled respiration when incubating P301L tau mitochondria either with oligomeric or fibrillar preparations of Abeta42. Finally, we found that aging specifically increased the sensitivity of mitochondria to oligomeric Abeta42 damage indicating that oligomeric and fibrillar Abeta42 are both toxic, but exert different degrees of toxicity.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
UniBasel Contributors:Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Springer
ISSN:0946-2716
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:18

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