Oligomeric and fibrillar species of β-amyloid (Aβ42) both impair mitochondrial function in P301L tau transgenic mice

Eckert, Anne, Hauptmann, Susanne, Scherping, Isabel, Meinhardt, Jessica, Rhein, Virginie, Drose, Stefan, Brandt, Ulrich, Fandrich, Marcus, Muller, Walter E. and Gotz, Jürgen (2008) Oligomeric and fibrillar species of β-amyloid (Aβ42) both impair mitochondrial function in P301L tau transgenic mice. Journal of Molecular Medicine, 86 11: 1255-1267. doi:10.1007/s00109-008-0391-6


Author Eckert, Anne
Hauptmann, Susanne
Scherping, Isabel
Meinhardt, Jessica
Rhein, Virginie
Drose, Stefan
Brandt, Ulrich
Fandrich, Marcus
Muller, Walter E.
Gotz, Jürgen
Title Oligomeric and fibrillar species of β-amyloid (Aβ42) both impair mitochondrial function in P301L tau transgenic mice
Journal name Journal of Molecular Medicine   Check publisher's open access policy
ISSN 0946-2716
1432-1440
Publication date 2008-01-01
Sub-type Article (original research)
DOI 10.1007/s00109-008-0391-6
Volume 86
Issue 11
Start page 1255
End page 1267
Total pages 13
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
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 Aβ peptide-containing plaques. When we addressed the role of Aβ, this indicated a synergistic action of tau and Aβ pathology on the mitochondria. In the present study, we compared the toxicity of different Aβ42 conformations in light of recent studies suggesting that oligomeric rather than fibrillar Aβ might be the actual toxic species. Interestingly, both oligomeric and fibrillar, but not disaggregated (mainly monomeric) Aβ42 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 Aβ42. Finally, we found that aging specifically increased the sensitivity of mitochondria to oligomeric Aβ42 damage indicating that oligomeric and fibrillar Aβ42 are both toxic, but exert different degrees of toxicity.
Keyword Alzheimer's disease
Amyloid β-peptide
Amyloid aggregates
Amyloid toxicity
Fibrils
Frontotemporal dementia
Globulomer
Mitochondria
Oligomer
Protein aggregation
Respiration
Tau
Transgenic mice
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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