Difference between revisions of "Eckert 2008 J Mol Med"

Latest revision as of 17:04, 19 February 2018

Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Dröse S, Brandt U, Fändrich M, Müller WE, Götz J (2008) Oligomeric and fibrillar species of beta-amyloid (Abeta42) both impair mitochondrial function in P301L tau transgenic mice. J Mol Med 86:1255-67.

» PMID: 18709343

Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Droese S, Brandt U, Faendrich M, Mueller WE, Goetz J (2008) J Mol Med

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. • Keywords: Alzheimer’s disease, Amyloid aggregates, Amyloid β-peptide, Amyloid toxicity, Fibrils, Frontotemporal dementia, Globulomer, Mitochondria, Oligomer, Protein aggregation, Respiration, Tau - Transgenic mice

• O2k-Network Lab: CH Basel Eckert A, NL Nijmegen Brandt U, DE Frankfurt Droese S, DE Frankfurt Eckert GP

Labels: MiParea: Respiration, Genetic knockout;overexpression Pathology: Neurodegenerative

Organism: Mouse Tissue;cell: Nervous system Preparation: Isolated mitochondria

HRR: Oxygraph-2k

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 {{Publication
-|title=Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Dröse S, Brandt U, Fändrich M, Müller WE, Götz J (2008) Oligomeric and fibrillar species of beta-amyloid (Abeta42) both impair mitochondrial function in P301L tau transgenic mice. J Mol Med 86: 1255-1267.
+|title=Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Dröse S, Brandt U, Fändrich M, Müller WE, Götz J (2008) Oligomeric and fibrillar species of beta-amyloid (Abeta42) both impair mitochondrial function in P301L tau transgenic mice. J Mol Med 86:1255-67.
 |info=[http://www.ncbi.nlm.nih.gov/pubmed/18709343 PMID: 18709343]
 |authors=Eckert A, Hauptmann S, Scherping I, Meinhardt J, Rhein V, Droese S, Brandt U, Faendrich M, Mueller WE, Goetz J
 |year=2008
 |journal=J Mol Med
-|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.
+|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.
 |keywords=Alzheimer’s disease,  Amyloid aggregates, Amyloid β-peptide, Amyloid toxicity, Fibrils, Frontotemporal dementia, Globulomer, Mitochondria, Oligomer, Protein aggregation, Respiration, Tau - Transgenic mice
-|mipnetlab=CH_Basel_Eckert A, DE_Frankfurt_Brandt U
+|mipnetlab=CH Basel Eckert A, NL Nijmegen Brandt U, DE Frankfurt Droese S, DE Frankfurt Eckert GP
 |discipline=Mitochondrial Physiology, Biomedicine, Environmental Physiology; Toxicology, Pharmacology; Biotechnology
 }}
 {{Labeling
+|area=Respiration, Genetic knockout;overexpression
+|organism=Mouse
+|tissues=Nervous system
+|preparations=Isolated mitochondria
+|diseases=Neurodegenerative
 |instruments=Oxygraph-2k
-|injuries=Mitochondrial Disease; Degenerative Disease and Defect, Genetic Defect; Knockdown; Overexpression
-|organism=Mouse
-|tissues=Neurons; Brain
-|preparations=Isolated Mitochondria
 |discipline=Mitochondrial Physiology, Biomedicine, Environmental Physiology; Toxicology, Pharmacology; Biotechnology
 }}