Hauptmann 2009 Neurobiol Aging
| Hauptmann S, Scherping I, Dröse S, Brandt U, Schulz KL, Jendrach M, Leuner K, Eckert A, Müller WE (2009) Mitochondrial dysfunction: An early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiol Aging 30:1574-86. |
Hauptmann S, Scherping I, Droese S, Brandt U, Schulz KL, Jendrach M, Leuner K, Eckert A, Mueller WE (2009) Neurobiol Aging
Abstract: Recent evidence suggests mitochondrial dysfunction as a common early pathomechanism in Alzheimer's disease integrating genetic factors related to enhanced amyloid-beta (Aß) production and tau-hyperphosphorylation with aging, as the most relevant sporadic risk factor. To further clarify the synergistic effects of aging and Aß pathology, we used isolated mitochondria of double Swedish and London mutant APP transgenic mice and of non-tg littermates. Pronounced mitochondrial dysfunction in adult Thy-1 APP mice, such as a drop of mitochondrial membrane potential and reduced ATP-levels already appeared at 3 months when elevated intracellular but not extracellular Aß deposits are present. Mitochondrial dysfunction was associated with higher levels of reactive oxygen species, an altered Bcl-xL/Bax ratio and reduction of COX IV activity. We observed significant decreases in state 3 respiration and FCCP-uncoupled respiration in non-tg mice after treatment with extracellular Aß. Similar deficits were seen only in aged Thy-1 APP mice, probably due to compensation within the respiratory chain in young animals. We conclude that Aß dependent mitochondrial dysfunction starts already at 3 months in this AD model before extracellular deposition of Aß and progression accelerates substantially with aging. • Keywords: Alzheimer's disease, APP mutation, Aging
• 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, mt-Medicine
Pathology: Aging;senescence, Alzheimer's, Neurodegenerative
Stress:Oxidative stress;RONS
Organism: Mouse
Tissue;cell: Nervous system
Preparation: Isolated mitochondria
HRR: Oxygraph-2k
