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Oligomeric and fibrillar species of beta-amyloid (A beta 42) both impair mitochondrial function in P301L tau transgenic mice

Eckert, Anne and Hauptmann, Susanne and Scherping, Isabel and Meinhardt, Jessica and Rhein, Virginie and Dröse, Stefan and Brandt, Ulrich and Fändrich, Marcus and Müller, Walter E. and Götz, Jürgen. (2008) Oligomeric and fibrillar species of beta-amyloid (A beta 42) 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/A5253438

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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 A beta peptide-containing plaques. When we addressed the role of A beta, this indicated a synergistic action of tau and A beta pathology on the mitochondria. In the present study, we compared the toxicity of different A beta 42 conformations in light of recent studies suggesting that oligomeric rather than fibrillar A beta might be the actual toxic species. Interestingly, both oligomeric and fibrillar, but not disaggregated (mainly monomeric) A beta 42 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 A beta 42. Finally, we found that aging specifically increased the sensitivity of mitochondria to oligomeric A beta 42 damage indicating that oligomeric and fibrillar A beta 42 are both toxic, but exert different degrees of toxicity.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK
UniBasel Contributors:Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Springer
ISSN:0946-2716
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Mar 2012 14:23
Deposited On:22 Mar 2012 13:36

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